Browsing by Author "Orostica, Karen"

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    Early-life nutrition interacts with developmental genes to shape the brain and sleep behavior in Drosophila melanogaster
    (2023) Olivares, Gonzalo H.; Nunez-Villegas, Franco; Candia, Noemi; Orostica, Karen; Gonzalez-Ramirez, M. Constanza; Vega-Macaya, Franco; Zuniga, Nolberto; Molina, Cristian; Oliva, Carlos; Mackay, Trudy F. C.; Verdugo, Ricardo A.; Olguin, Patricio
    The mechanisms by which the genotype interacts with nutrition during development to contribute to the variation of complex behaviors and brain morphology of adults are not well understood. Here we use the Drosophila Genetic Reference Panel to identify genes and pathways underlying these interactions in sleep behavior and mushroom body morphology. We show that early-life nutritional restriction effects on sleep behavior and brain morphology depends on the genotype. We mapped genes associated with sleep sensitivity to early-life nutrition, which were enriched for protein-protein interactions responsible for translation, endocytosis regulation, ubiquitination, lipid metabolism, and neural development. By manipulating the expression of candidate genes in the mushroom bodies (MBs) and all neurons, we confirm that genes regulating neural development, translation and insulin signaling contribute to the variable response of sleep and brain morphology to early-life nutrition. We show that the interaction between differential expression of candidate genes with nutritional restriction in early life resides in the MBs or other neurons and that these effects are sex-specific. Natural variations in genes that control the systemic response to nutrition and brain development and function interact with early-life nutrition in different types of neurons to contribute to the variation of brain morphology and adult sleep behavior.
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    Exploring the clinical and genetical spectrum of ADPKD in Chile to assess ProPKD score as a risk prediction tool
    (2023) Bayyad, Esperanza; Plaza, Anita; Klenner, Jaime; Downey Concha, Patricio; Salas, Paulina; Maragaño, Daniela; Herrera, Patricio; Lehmann, Paula; Quiroz, Lily; Zavala, María J.; Orostica, Karen; Flores, Claudio; Ardiles, Leopoldo; Maturana, Jorge; Krall, Paola
    Background Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited condition associated primarily with PKD1 and PKD2 genes. However, ADPKD patients in Latin America have had limited access to comprehensive care. The ProPKD score predicts the likelihood of kidney failure before the age of 60. This study aimed to describe the clinical and genetic characteristics of Chilean ADPKD patients and assess the ProPKD score. Methods We enrolled 40 ADPKD probands and 122 relatives from different centers. Genetic analysis of PKD1 and PKD2 genes was performed by combining direct and next-generation sequencing. Pathogenicity was determined using bioinformatic tools. ProPKD scores were calculated based on clinical and genetic data. Results ADPKD probands were diagnosed at a median age of 35 years. Pathogenic, likely pathogenic, or uncertain significance variants were identified in 38/40 pedigrees, with 89% involving PKD1 and 11% involving PKD2 variants. Among the identified variants, 62% were novel. Patients with PKD1 truncating variants had a more severe disease course, reaching kidney failure by a median age of 48.5 years. ProPKD scores were assessed in 72 individuals, stratifying them into high-, intermediate-, or low-risk categories and the median ages for kidney failure were 45, 49, and 52 years, respectively (log-rank p = 0.001). Conclusion This study provides valuable insights into the clinical and genetic profiles of ADPKD patients in Chile. ADPKD poses a significant public health concern, warranting improvements in diagnosis and treatment. The use of the ProPKD score to predict disease progression should be further explored to enhance patient care and management.