Browsing by Author "Eyheramendy, Susana"
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Item Adaptation to Extreme Environments in an Admixed Human Population from the Atacama Desert(2019) Vicuña, Lucas; Fernández, Mario; Vial, Cecilia; Valdebenito, Patricio; Chaparro, Eduardo; Espinoza, Karena; Ziegler, Annmarie; Bustamante, Alberto; Eyheramendy, SusanaInorganic arsenic (As) is a toxic xenobiotic and carcinogen associated with severe health conditions. The urban population from the Atacama Desert in northern Chile was exposed to extremely high As levels(upto600 mg/l)in drink ing water between 1958 and 1971, leading to increased incidence of urinary bladder cancer (BC), skin cancer, kidney cancer, and coronary thrombosis decades later. Besides, the Andean Native-American ancestors of the Atacama population were previously exposed for millennia to elevated As levels in water (120 mg/l) for at least 5,000 years, suggesting adaptation to this selective pressure. Here, we performed two genome-wide selection tests—PBSn1 and an ancestry-enrichment test—in an admixed population from Atacama, to identify adaptation signatures to As exposure acquired before and after admixture with Europeans, respectively. The top second variant selected by PBSn1 was associated with LCE4A-C1orf68, a gene that may be involved in the immune barrier of the epithelium during BC. We performed association tests between the top PBSn1 hits and BC occurrence in our population. The strongest association (P1⁄4 0.012) was achieved by the LCE4A-C1orf68 variant. The ancestry-enrichment test detected highly significant signals (P1⁄4 1.3 109 ) mapping MAK16, a gene with important roles in ribosome biogenesis during the G1 phase of the cell cycle. Our results contribute to a better understanding of the genetic factors involved in adaptation to the pathophysiological consequences of As exposure.Item Genetic structure characterization of Chileans reflects historical immigration patterns(Macmillan Publishers Limited, 2015) Eyheramendy, Susana; Martínez, Felipe; Manevy, Federico; Vial, Cecilia; Repetto, GabrielaIdentifying the ancestral components of genomes of admixed individuals helps uncovering the genetic basis of diseases and understanding the demographic history of populations. We estimate local ancestry on 313 Chileans and assess the contribution from three continental populations. The distribution of ancestry block-length suggests an average admixing time around 10 generations ago. Sex-chromosome analyses confirm imbalanced contribution of European men and Native-American women. Previously known genes under selection contain SNPs showing large difference in allele frequencies. Furthermore, we show that assessing ancestry is harder at SNPs with higher recombination rates and easier at SNPs with large difference in allele frequencies at the ancestral populations. Two observations, that African ancestry proportions systematically decrease from North to South, and that European ancestry proportions are highest in central regions, show that the genetic structure of Chileans is under the influence of a diffusion process leading to an ancestry gradient related to geography.Item Postadmixture Selection On Chileans Targets Haplotype Involved In Pigmentation, Thermogenesis And Immune Defense Against Pathogens(2020-06) Vicuña, Lucas; Klimenkova, Olga; Norambuena, Tomás; Martínez, Felipe; Shchur, Vladimir; Eyheramendy, Susana; Fernández, Mario I.Detection of positive selection signatures in populations around the world is helping to uncover recent human evolutionary history as well as the genetic basis of diseases. Most human evolutionary genomic studies have been performed in European, African, and Asian populations. However, populations with Native American ancestry have been largely underrepresented. Here, we used a genome-wide local ancestry enrichment approach complemented with neutral simulations to identify postadmixture adaptations underwent by admixed Chileans through gene flow from Europeans into local Native Americans. The top significant hits (P=2.4x10(-7)) are variants in a region on chromosome 12 comprising multiple regulatory elements. This region includes rs12821256, which regulates the expression of KITLG, a well-known gene involved in lighter hair and skin pigmentation in Europeans as well as in thermogenesis. Another variant from that region is associated with the long noncoding RNA RP11-13A1.1, which has been specifically involved in the innate immune response against infectious pathogens. Our results suggest that these genes were relevant for adaptation in Chileans following the Columbian exchange.Item Screening of COVID-19 cases through a Bayesian network symptoms model and psychophysical olfactory test(2021) Eyheramendy, Susana; Saa, Pedro A.; Undurraga, Eduardo A.; Valencia, Carlos; López, Carolina; Méndez Alcamán, Luis; Pizarro-Berdichevsky, Javier; Finkelstein-Kulka, Andrés; Solari, Sandra; Salas, Nicolás; Bahamondes, Pedro; Ugarte, Martín; Barceló, Pablo; Arenas, Marcelo; Agosin, EduardoThe sudden loss of smell is among the earliest and most prevalent symptoms of COVID-19 when measured with a clinical psychophysical test. Research has shown the potential impact of frequent screening for olfactory dysfunction, but existing tests are expensive and time consuming. We developed a low-cost ($0.50/test) rapid psychophysical olfactory test (KOR) for frequent testing and a model-based COVID-19 screening framework using a Bayes Network symptoms model. We trained and validated the model on two samples: suspected COVID-19 cases in five healthcare centers (n = 926; 33% prevalence, 309 RT-PCR confirmed) and healthy miners (n = 1,365; 1.1% prevalence, 15 RT-PCR confirmed). The model predicted COVID-19 status with 76% and 96% accuracy in the healthcare and miners samples, respectively (healthcare: AUC = 0.79 [0.75–0.82], sensitivity: 59%, specificity: 87%; miners: AUC = 0.71 [0.63–0.79], sensitivity: 40%, specificity: 97%, at 0.50 infection probability threshold). Our results highlight the potential for low-cost, frequent, accessible, routine COVID-19 testing to support society's reopening.