Browsing by Author "Azócar López, Lorena Karina"

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    Flow studies on human GPVI-deficient blood under coagulating and noncoagulating conditions
    (2020) Nagy, Magdolna; Perrella, Gina; Dalby, Amanda; Becerra Yañez, María Francisca Aurora del Car; García Quintanilla, Lourdes; Pike, Jeremy A.; Morgan, Neil V.; Gardiner, Elizabeth E.; Heemskerk, Johan W. M.; Azócar López, Lorena Karina; Miquel Poblete, Juan Francisco; Mezzano Abedrapo, Diego; Watson, Steve P.
    The role of glycoprotein VI (GPVI) in platelets was investigated in 3 families bearing an insertion within the GP6 gene that introduces a premature stop codon prior to the transmembrane domain, leading to expression of a truncated protein in the cytoplasm devoid of the transmembrane region. Western blotting and flow cytometry of GP6(hom) (homozygous) platelets confirmed loss of the full protein. The level of the Fc receptor -gamma-chain, which associates with GPVI in the membrane, was partially reduced, but expression of other receptors and signaling proteins was not altered. Spreading of platelets on collagen and von Willebrand factor (which supports partial spreading) was abolished in GP6(hom) platelets, and spreading on uncoated glass was reduced. Anticoagulated whole blood flowed over immobilized collagen or a mixture of von Willebrand factor, laminin, and rhodocytin (noncollagen surface) generated stable platelet aggregates that express phosphatidylserine (PS). Both responses were blocked on the 2 surfaces in GP6(hom) individuals, but adhesion was not altered. Thrombin generation was partially reduced in GP6(hom) blood. The frequency of the GP6(het) (heterozygous) variant in a representative sample of the Chilean population (1212 donors) is 2.9%, indicating that there are similar to 4000 GP6(hom) individuals in Chile. These results demonstrate that GPVI supports aggregation and PS exposure under flow on collagen and noncollagen surfaces, but not adhesion. The retention of adhesion may contribute to the mild bleeding diathesis of GP6(hom) patients and account for why so few of the estimated 4000 GP6(hom) individuals in Chile have been identified.
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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