Biology subjects

Garcia-Garcia, L.

Publications and source records attributed to Garcia-Garcia, L..

3 recordsLinked to original sources

bioRxiv2022

Nationwide genomic biobank in Mexico unravels demographic history and complex trait architecture from 6,057 individuals

Latin America continues to be severely underrepresented in genomics research, and fine-scale genetic histories as well as complex trait architectures remain hidden due to the lack of Big Data. To fill this gap, the Mexican Biobank project genotyped 1.8 million markers in 6,057 individuals from 32 states and 898 sampling localities across Mexico with linked complex trait and disease information creating a valuable nationwide genotype-phenotype database. Through a suite of state-of-the-art methods for ancestry deconvolution and inference of identity-by-descent (IBD) segments, we inferred detailed ancestral histories for the last 200 generations in different Mesoamerican regions, unraveling native and colonial/post-colonial demographic dynamics. We observed large variations in runs of homozygosity (ROH) among genomic regions with different ancestral origins reflecting their demographic histories, which also affect the distribution of rare deleterious variants across Mexico. We analyzed a range of biomedical complex traits and identified significant genetic and environmental factors explaining their variation, such as ROH found to be significant predictors for trait variation in BMI and triglycerides.

genomics↗

bioRxiv2022

Adenine base editing is an efficient approach to restore function in FA patient cells without double-stranded DNA breaks

Fanconi Anemia (FA) is a debilitating genetic disorder with a wide range of severe symptoms including bone marrow failure and predisposition to cancer. CRISPR-Cas genome editing manipulates genotypes by harnessing DNA repair and has been proposed as a potential cure for FA. But FA is caused deficiencies in DNA repair itself, preventing the use of editing strategies such as homology directed repair. Recently developed base editing (BE) systems do not rely on double stranded DNA breaks and might be used to target mutations in FA genes, but this remains to be tested. Here we develop a proof of concept therapeutic base editing strategy to address two of the most prevalent FANCA mutations in patient cells. We find that optimizing adenine base editor construct, vector type, guide RNA format, and delivery conditions lead to very effective genetic modification in multiple FA patient backgrounds. Optimized base editing restored FANCA expression, molecular function of the FA pathway, and phenotypic resistance to crosslinking agents. ABE8e mediated editing in primary hematopoietic stem and progenitor cells from an FA patient was both genotypically effective and restored FA pathway function, indicating the potential of base editing strategies for future clinical application in FA.

molecular biology↗

bioRxiv2020

The multidisciplinary nature of COVID-19 research

ObjectiveWe analyzed the scientific output after COVID-19 and contrasted it with studies published in the aftermath of seven epidemics/pandemics: Severe Acute Respiratory Syndrome (SARS), Influenza A virus H5N1 and Influenza A virus H1N1 human infections, Middle East Respiratory Syndrome (MERS), Ebola virus disease, Zika virus disease, and Dengue. Design/Methodology/ApproachWe examined bibliometric measures for COVID-19 and the rest of studied epidemics/pandemics. Data were extracted from Web of Science, using its journal classification scheme as a proxy to quantify the multidisciplinary coverage of scientific output. We proposed a novel Thematic Dispersion Index (TDI) for the analysis of pandemic early stages. Results/DiscussionThe literature on the seven epidemics/pandemics before COVID-19 has shown explosive growth of the scientific production and continuous impact during the first three years following each emergence or re-emergence of the specific infectious disease. A subsequent decline was observed with the progressive control of each health emergency. We observed an unprecedented growth in COVID-19 scientific production. TDI measured for COVID-19 (29,4) in just six months, was higher than TDI of the rest (7,5 to 21) during the first three years after epidemic initiation. ConclusionsCOVID-19 literature showed the broadest subject coverage, which is clearly a consecuence of its social, economic, and political impact. The proposed indicator (TDI), allowed the study of multidisciplinarity, differentiating the thematic complexity of COVID-19 from the previous seven epidemics/pandemics. Originality/ValueThe multidisciplinary nature and thematic complexity of COVID-19 research were successfully analyzed through a scientometric perspective.

scientific communication and education↗