Biology subjects

Ortiz, D.

Publications and source records attributed to Ortiz, D..

3 recordsLinked to original sources

bioRxiv2018

Loss-of-function in IRF2BPL is associated with neurological phenotypes

The Interferon Regulatory Factor 2 Binding Protein Like (IRF2BPL) gene encodes a member of the IRF2BP family of transcriptional regulators. Currently the biological function of this gene is obscure, and the gene has not been associated with a Mendelian disease. Here we describe seven individuals affected with neurological symptoms who carry damaging heterozygous variants in IRF2BPL. Five cases carrying nonsense variants in IRF2BPL resulting in a premature stop codon display severe neurodevelopmental regression, hypotonia, progressive ataxia, seizures, and a lack of coordination. Two additional individuals, both with missense variants, display global developmental delay and seizures and a relatively milder phenotype than those with nonsense alleles. The bioinformatics signature for IRF2BPL based on population genomics is consistent with a gene that is intolerant to variation. We show that the IRF2BPL ortholog in the fruit fly, called pits (protein interacting with Ttk69 and Sin3A), is broadly expressed including the nervous system. Complete loss of pits is lethal early in development, whereas partial knock-down with RNA interference in neurons leads to neurodegeneration, revealing requirement for this gene in proper neuronal function and maintenance. The nonsense variants in IRF2BPL identified in patients behave as severe loss-of-function alleles in this model organism, while ectopic expression of the missense variants leads to a range of phenotypes. Taken together, IRF2BPL and pits are required in the nervous system in humans and flies, and their loss leads to a range of neurological phenotypes in both species.

genetics↗

bioRxiv2018

Consumption of carotenoids not increased by bacterial infection in brown trout embryos (Salmo trutta)

Carotenoids are organic pigment molecules that play important roles in signalling, control of oxidative stress, and immunity. Fish allocate carotenoids to their eggs, which gives them the typical yellow to red colouration and supports their resistance against microbial infections. However, it is still unclear whether carotenoids act mainly as a shield against infection or are used up during the embryos immune defence. We investigated this question with experimental families produced from wild-caught brown trout (Salmo trutta). Singly raised embryos were either exposed to the bacterial pathogen Pseudomonas fluorescens or sham-treated at one of two stages during their development. A previous study on these experimental families reported positive effects of egg carotenoids on embryo growth and resistance against the infection. Here, we quantified carotenoid consumption in these infected and sham-infected maternal sib groups. We found that carotenoid contents mostly decreased during embryogenesis. However, these decreases were neither linked to the virulence induced by the pathogen nor dependent on the time point of infection. We conclude that egg carotenoids are not significantly used up by the embryos immune defence.

ecology↗

bioRxiv2017

Pleiotropy in enhancer function is encoded through diverse genetic architectures

Developmental genes can have complex c/s-regulatory regions, with multiple enhancers scattered across stretches of DNA spanning tens or hundreds of kilobases. Early work revealed remarkable modularity of enhancers, where distinct regions of DNA, bound by combinations of transcription factors, drive gene expression in defined spatio-temporal domains. Nevertheless, a few reports have shown that enhancer function may be required in multiple developmental stages, implying that regulatory elements can be pleiotropic. In these cases, it is not clear whether the pleiotropic enhancers employ the same transcription factor binding sites to drive expression at multiple developmental stages or whether enhancers function as chromatin scaffolds, where independent sets of transcription factor binding sites act at different stages. In this work we have studied the activity of the enhancers of the shavenbaby gene throughout D. melanogaster development. We found that all seven shavenbaby enhancers drive gene expression in multiple tissues and developmental stages at varying levels of redundancy. We have explored how this pleiotropy is encoded in two of these enhancers. In one enhancer, the same transcription factor binding sites contribute to embryonic and pupal expression, whereas for a second enhancer, these roles are largely encoded by distinct transcription factor binding sites. Our data suggest that enhancer pleiotropy might be a common feature of c/s-regulatory regions of developmental genes and that this pleiotropy can be encoded through multiple genetic architectures.

genetics↗