Biology subjects

Arboleda, H.

Publications and source records attributed to Arboleda, H..

3 recordsLinked to original sources

bioRxiv2023

Genetics of Latin American Diversity (GLAD) Project: insights into population genetics and association studies in recently admixed groups in the Americas

Latin America is underrepresented in genetic studies, which can exacerbate disparities in personalized genomic medicine. However, genetic data of thousands of Latin Americans are already publicly available, but require a bureaucratic maze to navigate all the data access and consenting issues. We present the Genetics of Latin American Diversity (GLAD) Project, a platform that compiles genome-wide information of 54,077 Latin Americans from 39 studies representing 45 geographical regions. Through GLAD, we identified heterogeneous ancestry composition and recent gene-flow across the Americas. Also, we developed a simulated-annealing-based algorithm to match the genetic background of external samples to our database and share summary statistics without transferring individual-level data. Finally, we demonstrate the potential of GLAD as a critical resource for evaluating statistical genetic softwares in the presence of admixture. By making this resource available, we promote genomic research in Latin Americans and contribute to the promises of personalized medicine to more people.

genetics↗

bioRxiv2020

Nucleolar disruption, activation of P53 and premature senescence in POLR3A-mutated Wiedemann-Rautenstrauch Syndrome fibroblasts

Recently, mutations in the RNA polymerase III subunit 3A (POLR3A) have been described as the cause of the neonatal progeria or Wiedemann-Rautenstrauch syndrome (WRS). POLR3A have important roles in the regulation of transcription of small RNAs, including tRNA, 5S rRNA and U6 snRNA. We aim to describe cellular and molecular features of WRS fibroblasts. Cultures of primary fibroblasts from one WRS patient [monoallelic POLR3A variant c.3772_3773delCT (p.Leu1258Glyfs*12)] and one control were grown. Mutation in POLR3A causes a decreased in the expression of POLR3A mRNA and protein and a sharp increased of mutant protein. In addition, there was an increased in its nuclear localization. These changes were associated to an increase number and area of nucleoli, a significantly larger nuclear area, and a high increased in the expression of pP53 and pH2AX. All these changes were associated to premature senescence. The present observations add to our understanding of the differences between HGPS and WRS, and opens new alternatives to study cell senesce and human aging.

cell biology↗

bioRxiv2018

ADHD: relation between cognitive characteristics and DAT1 / DRD4 dopamine polymorphisms

Attention deficit hyperactivity disorder (ADHD) is a clinical and diagnostic heterogeneous picture. This study analysed the association of functional polymorphisms in DAT1 VNTR 3 UTR and DRD4 VNTR Exon III candidate genes, and the neuropsychological characterisation of attention and executive functions of a group of children with ADHD vs. controls. 32 patients and 51 controls were selected. The DAT1 10-repeat allele appeared more frequently in the two groups (cases: 0.93/control: 0.82), showing an OR: 2.5 (IC 95%: 0.684-9.133; p: 0.158). In DRD4, the 4-repeat allele shows the highest occurrence (cases: 0.62/controls: 0.60). None of the markers presented a significant association after a direct analysis, but the DRD4 7-repeat marker showed a positive risk when performing a Bayesian logistic analysis (coefficient: -1.69; OR: 5.39 CI 95%: 1.167-40.97). On the other hand, when considering association with cognitive performance, a positive risk for processing speed and attention tasks was identified.

neuroscience↗