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Author: search.filters.author.Francisco A. CubillosSubject: search.filters.subject.precision medicine

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    Item type:Publication,
    Genomic modifiers of neurological resilience in a Niemann‐Pick C family
    (Wiley, 2025-06-12)
    Macarena Las Heras
    ;
    Benjamín Szenfeld
    ;
    Valeria Olguín
    ;
    Juan Carlos Rubilar
    ;
    CALDERON GIADROSIC, JUAN FRANCISCO  
    Niemann-Pick type C (NPC) disease, caused by NPC1 or NPC2 variants, disrupts cholesterol and glycolipid trafficking, leading to diverse clinical manifestations. To understand the genetic basis of neurological resilience, we analyzed an NPC family with variable phenotypes, identifying loss-of-function variants in CCDC115, SLC4A5, DEPDC5, ETFDH, SNRNP200, and DOCK1 that co-segregated with milder neurological involvement. Using yeast models, we successfully predicted NPC-like severity based on orthologous gene variants. RNA-seq revealed a positive correlation between mitochondrial transcripts and cellular fitness. Modeling NPC in yeast lacking the SLC4A5 ortholog, bor1, enhanced cellular fitness, improved mitochondrial function, and reduced sterol accumulation. Our findings identify potential modifiers and biomarkers of NPC severity, highlighting mitochondrial pathways and SLC4A5 as a therapeutic target.
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    Item type:Publication,
    Genetic Background Matters: Population-Based Studies in Model Organisms for Translational Research
    (2022)
    Valeria Olguín
    ;
    Anyelo Durán
    ;
    Macarena Las Heras
    ;
    Juan Carlos Rubilar
    ;
    Francisco A. Cubillos
    <jats:p>We are all similar but a bit different. These differences are partially due to variations in our genomes and are related to the heterogeneity of symptoms and responses to treatments that patients exhibit. Most animal studies are performed in one single strain with one manipulation. However, due to the lack of variability, therapies are not always reproducible when treatments are translated to humans. Panels of already sequenced organisms are valuable tools for mimicking human phenotypic heterogeneities and gene mapping. This review summarizes the current knowledge of mouse, fly, and yeast panels with insightful applications for translational research.</jats:p>
      46Scopus© Citations 8