Browsing by Author "Riveras, Eleodoro"

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    Common variants in ABCG8 and TRAF3 genes confer risk for gallstone disease and gallbladder cancer in admixed Latinos with Mapuche Native American ancestry
    (2018) Bustos, Bernabé I.; Pérez Palma, Eduardo; Buch, Stephan; Azócar, Lorena; Riveras, Eleodoro; Ugarte, Giorgia D.; Toliat, Mohammad; Nürnberg, Peter; Lieb, Wolfgang; Franke, Andre; Hinz, Sebastian; Burmeister, Greta; von Schönfels, Witigo; Schafmayer, Clemens; Völzke, Henry; Völker, Uwe; Homuth, Georg; Lerch, Markus M.; Santos Martín, José Luis; Puschel Illanes, Klaus; Bambs S., Claudia; Gutiérrez Ilabaca, Rodrigo Antonio; Hampe, Jochen; de Ferrari, Giancarlo V.; Miquel, Juan Francisco
    Background Latin Americans and Chilean Amerindians have the highest prevalence of cholesterol gallstone disease (GSD) and gallbladder cancer (GBC) in the world. A handful of loci have been associated with GSD in populations of predominantly European ancestry, however they only explain a small portion of the population-attributable risk of the disease.Methods We performed a genome-wide association study (GWAS) for GSD in 1,095 admixed Latinos with Mapuche Native American Ancestry, followed by a replication analysis of 10 candidate single nucleotide polymorphisms (SNPs) with suggestive genome-wide significance (P<1×10−5) in 1,643 individuals. Disease status was assessed by cholecystectomy or abdominal ultrasonography. Logistic regression analyses were adjusted for age, sex, BMI, Type 2 Diabetes and Amerindian ancestry. Associated variants were further examined in two large GSD European populations and in a Chilean gallbladder cancer (GBC) cohort. We determined the expression levels of a novel GSD-candidate gene in normal and GSD-tissue samples.Results We consistently replicated the ABCG8 gene (rs11887534; P=3.24×10−8, OR=1.74) associated with GSD in admixed Latinos and identified a novel candidate signal within the TRAF3 gene on chromosome 14 (rs12882491; P=1.11×10−7, OR=1.40). ABCG8 and TRAF3 variants also conferred risk to GBC. Gene expression analyses indicated that TRAF3 levels were significantly decreased in the gallbladder (P=0.015) and the duodenal mucosa (P=0.001) of affected GSD individuals compared to healthy controls.Conclusions We confirmed ABCG8 and identified TRAF3 both associated with GSD and GBC in admixed Latinos. Decreased TRAF3 expression levels could enhance gallbladder inflammation as is observed in GSD and GSD-associated GBC.
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    Dynamic changes in mRNA nucleocytoplasmic localization in the nitrate response of Arabidopsis roots
    (2024) Fonseca, Alejandro; Riveras, Eleodoro; Moyano, Tomas C.; Alvarez, Jose M.; Rosa, Stefanie; Gutierrez, Rodrigo A.
    Nitrate is a nutrient and signal that regulates gene expression. The nitrate response has been extensively characterized at the organism, organ, and cell-type-specific levels, but intracellular mRNA dynamics remain unexplored. To characterize nuclear and cytoplasmic transcriptome dynamics in response to nitrate, we performed a time-course expression analysis after nitrate treatment in isolated nuclei, cytoplasm, and whole roots. We identified 402 differentially localized transcripts (DLTs) in response to nitrate treatment. Induced DLT genes showed rapid and transient recruitment of the RNA polymerase II, together with an increase in the mRNA turnover rates. DLTs code for genes involved in metabolic processes, localization, and response to stimulus indicating DLTs include genes with relevant functions for the nitrate response that have not been previously identified. Using single-molecule RNA FISH, we observed early nuclear accumulation of the NITRATE REDUCTASE 1 (NIA1) transcripts in their transcription sites. We found that transcription of NIA1, a gene showing delayed cytoplasmic accumulation, is rapidly and transiently activated; however, its transcripts become unstable when they reach the cytoplasm. Our study reveals the dynamic localization of mRNAs between the nucleus and cytoplasm as an emerging feature in the temporal control of gene expression in response to nitrate treatment in Arabidopsis roots.
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    Spatiotemporal analysis identifies ABF2 and ABF3 as key hubs of endodermal response to nitrate
    (2022) Contreras-Lopez, Orlando; Vidal, Elena A.; Riveras, Eleodoro; Alvarez, Jose M.; Moyano, Tomas C.; Sparks, Erin E.; Medina, Joaquin; Pasquino, Angelo; Benfey, Philip N.; Coruzzi, Gloria M.; Gutierrez, Rodrigo A.
    Nitrate is a nutrient and a potent signal that impacts global gene expression in plants. However, the regulatory factors controlling temporal and cell type-specific nitrate responses remain largely unknown. We assayed nitrate-responsive transcriptome changes in five major root cell types of the Arabidopsis thaliana root as a function of time. We found that gene-expression response to nitrate is dynamic and highly localized and predicted cell type- specific transcription factor (TF)-target interactions. Among cell types, the endodermis stands out as having the largest and most connected nitrate-regulatory gene network. ABF2 and ABF3 are major hubs for transcriptional responses in the endodermis cell layer. We experimentally validated TF-target interactions for ABF2 and ABF3 by chromatin immunoprecipitation followed by sequenc-ing and a cell-based system to detect TF regulation genome-wide. Validated targets of ABF2 and ABF3 account for more than 50% of the nitrate-responsive transcriptome in the endodermis. Moreover, ABF2 and ABF3 are involved in nitrate-induced lateral root growth. Our approach offers an unprecedented spatiotemporal resolution of the root response to nitrate and identifies important compo-nents of cell-specific gene regulatory networks.
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    Whole genome sequence of Mapuche-Huilliche Native Americans
    (2018) Vidal Olate, Elena Alejandra; Moyano Yugovic, Tomás Custodio; Bustos, Bernabé I.; Pérez-Palma, Eduardo; Moraga Marín, Carol Mabel; Montecinos López, Alejandro; Azócar López, Lorena Karina; Soto Wilder, Daniela Constanza; Riveras, Eleodoro; Vidal, Mabel; Genova, Alex Di; Puschel Illanes, Klaus; Nürnberg, Peter; Buch, Stephan; Hampe, Jochen; Eyheramendy Duerr, Susana; Miquel Poblete, Juan Francisco; Gutiérrez Ilabaca, Rodrigo Antonio
    Background Whole human genome sequencing initiatives provide a compendium of genetic variants that help us understand population history and the basis of genetic diseases. Current data mostly focuses on Old World populations and information on the genomic structure of Native Americans, especially those from the Southern Cone is scant. Results Here we present a high-quality complete genome sequence of 11 Mapuche-Huilliche individuals (HUI) from Southern Chile (85% genomic and 98% exonic coverage at > 30X), with 96-97% high confidence calls. We found approximately 3.1x106 single nucleotide variants (SNVs) per individual and identified 403,383 (6.9%) of novel SNVs that are not included in current sequencing databases. Analyses of large-scale genomic events detected 680 copy number variants (CNVs) and 4,514 structural variants (SVs), including 398 and 1,910 novel events, respectively. Global ancestry composition of HUI genomes revealed that the cohort represents a marginally admixed population from the Southern Cone, whose genetic component is derived from early Native American ancestors. In addition, we found that HUI genomes display highly divergent and novel variants with potential functional impact that converge in ontological categories essential in cell metabolic processes. Conclusions Mapuche-Huilliche genomes contain a unique set of small- and large-scale genomic variants in functionally linked genes, which may contribute to susceptibility for the development of common complex diseases or traits in admixed Latinos and Native American populations. Our data represents an ancestral reference panel for population-based studies in Native and admixed Latin American populations