Biology subjects

Rodriguez, S.

Publications and source records attributed to Rodriguez, S..

4 recordsLinked to original sources

bioRxiv2018

A genome-wide association study of mitochondrial DNA copy number in two population-based cohorts

Mitochondrial DNA copy number (mtDNA CN) exhibits interindividual and intercellular variation, but few genome-wide association studies (GWAS) of directly assayed mtDNA CN exist.\n\nWe undertook a GWAS of qPCR-assayed mtDNA CN in the Avon Longitudinal Study of Parents and Children (ALSPAC), and the UK Blood Service (UKBS) cohort. After validating and harmonising data, 5461 ALSPAC mothers (16-43 years at mtDNA CN assay), and 1338 UKBS females (17-69 years) were included in a meta-analysis. Sensitivity analyses restricted to females with white cell-extracted DNA, and adjusted for estimated or assayed cell proportions. Associations were also explored in ALSPAC children, and UKBS males.\n\nA neutrophil-associated locus approached genome-wide significance (rs709591 [MED24], {beta}[SE] -0.084 [0.016], p=1.54e-07) in the main meta-analysis of adult females. This association was concordant in magnitude and direction in UKBS males and ALSPAC neonates. SNPs in and around ABHD8 were associated with mtDNA CN in ALSPAC neonates (rs10424198, {beta}[SE] 0.262 [0.034], p=1.40e-14), but not other study groups. In a meta-analysis of unrelated individuals (N=11253), we replicated a published association in TFAM {beta}[SE] 0.046 [0.017], p=0.006), with an effect size much smaller than that observed in the replication analysis of a previous in silico GWAS.\n\nIn a hypothesis-generating GWAS, we confirm an association between TFAM and mtDNA CN, and present putative loci requiring replication in much larger samples. We discuss the limitations of our work, in terms of measurement error and cellular heterogeneity, and highlight the need for larger studies to better understand nuclear genomic control of mtDNA copy number.

genomics↗

bioRxiv2018

Genome-encoded Cytoplasmic Double-Stranded RNAs, Found in C9ORF72 ALS-FTD Brain, Provoke Propagated Neuronal Death

Innate immune signaling activation and DNA damage are pathological hallmarks of aging that may herald multiple adult-onset neurodegenerative diseases. Here, we report that both cell autonomous and non-autonomous neuronal death are triggered by the production of cytoplasmic double-stranded RNA (cdsRNA) from a regulated, disarticulated transgene in the setting of type I interferon (IFN-I) signaling. CdsRNA is a pathogen associated molecular pattern that induces IFN-I in many cell types. Transfection of a dsRNA mimetic into cultured human neurons also induces IFN-I signaling and cell death in a dose-dependent manner. Direct relevance to human disease is found in neurons of ALS-FTD patients carrying C9ORF72 intronic hexanucleotide expansions; cdsRNA isolated from these tissues is comprised of repeat sequences. Together, these findings implicate cdsRNA generated from genomic sequences in neurons as a trigger for sterile, viral-mimetic IFN-I induction and propagated neuronal death within in a neural circuit in the aging nervous system.

neuroscience↗

bioRxiv2017

Hematology, biochemistry, and toxicology of wild hawksbill turtles (Eretmochelys imbricata) nesting in mangrove estuaries in the eastern Pacific Ocean

Sea turtles are a keystone species and are highly sensitive to changes in their environment, making them excellent environmental indicators. In light of environmental and climate changes, species are increasingly threatened by pollution, changes in ocean health, habitat alteration, and plastic ingestion. There may be additional health related threats and understanding these threats is key in directing future management and conservation efforts, particularly for severely reduced sea turtle populations. Hawksbill turtles (Eretmochelys imbricata) are critically endangered, with those in the eastern Pacific Ocean (Mexico-Peru) considered one of the most threatened sea turtle populations in the world. This study establishes baseline health parameters in hematology and blood biochemistry as well as tested for heavy metals and persitent organic pollutants in eastern Pacific hawksbills at a primary nesting colony located in a mangrove estuary. Whereas hematology and biochemistry results are consistent with healthy populations of other species of sea turtles, we identified differences in packed cell volume, heterophils and lympohcyte counts, and glucose when comparing our data to other adult hawksbill analysis (1), (2), (3). Our analysis of heavy metal contamination revealed a mean blood level of 0.245 ppm of arsenic, 0.045 ppm of lead, and 0.008 ppm of mercury. Blood levels of persistent organic pollutants were below the laboratory detection limit for all turtles. Our results suggest that differences in the feeding ecology of eastern Pacific hawksbills in mangrove estuaries may make them less likely to accumulate persistent organic pollutants and heavy metals in their blood. These baseline data on blood values in hawksbills nesting within a mangrove estuary in the eastern Pacific offer important guidance for health assessments of the species in the wild and in clinical rehabilitation facilities, and underscore the importance of preventing contamination from point and non-point sources in mangrove estuaries, which represent primary habitat to hawksbills and myriad other marine species in the eastern Pacific Ocean.

zoology↗

bioRxiv2017

The Impact of Education on Myopia: A bidirectional Mendelian randomisation analysis in UK Biobank

Myopia, or short-sightedness, is one of the leading causes of visual disability in the World. The prevalence of myopia has risen steadily over recent decades, reaching epidemic levels in Southeast Asia. Observational studies have reported associations between educational attainment and myopia. Whether education causes myopia, myopic children are more intelligent, or another factor, like higher socioeconomic status, causes both is unclear since observational studies are prone to confounding and randomised trials of education are unethical. Using bidirectional Mendelian Randomisation, a form of instrumental variable (IV) analysis free from confounding, we show that every additional year in education leads to an increase in myopic refractive error, but that myopia does not lead to higher educational attainment. Our results suggest that current educational methods contribute to the global burden of myopia, and argue that educational policies and practices should take account of this to reduce future visual disability in the population.

epidemiology↗