Biology subjects

Boughton, A.

Publications and source records attributed to Boughton, A..

2 recordsLinked to original sources

bioRxiv2021

FIVEx: an interactive multi-tissue eQTL browser

SummaryExpression quantitative trait loci (eQTLs) characterize the associations between genetic variation and gene expression to provide insights into tissue-specific gene regulation. Interactive visualization of tissue-specific eQTLs can facilitate our understanding of functional variants relevant to disease-related traits. However, combining the multi-dimensional nature of eQTLs into a concise and informative visualization is challenging. Existing eQTL visualization tools provide useful ways to summarize the unprecedented scale of transcriptomic data but are not necessarily tailored to answer questions about the functional interpretations of trait-associated variants or other variants of interest. We developed FIVEx, an interactive eQTL browser with an intuitive interface tailored to the functional interpretation of associated variants. It features the ability to navigate seamlessly between different data views while providing relevant tissue- and locus-specific information to offer users a better understanding of population-scale multi-tissue transcriptomic profiles. Our implementation of the FIVEx browser on the Gene-Tissue Expression (GTEx) dataset provides important insights for understanding potential tissue-specific regulatory mechanisms underlying trait-associated signals. Availability and implementationA FIVEx instance visualizing GTEx v8 data can be found at https://eqtl.pheweb.org. The FIVEx source code is open source under an MIT license at https://github.com/statgen/fivex.

bioinformatics↗

bioRxiv2019

Highly clustered de novo frameshift variants in the neuronal splicing factor NOVA2 result in a specific abnormal C terminal part and cause a severe form of intellectual disability with autistic features.

The Neuro-Oncological Ventral Antigen 2 NOVA2 protein is a major factor regulating neuron specific alternative splicing, previously associated with an acquired neurologic condition, the paraneoplastic opsoclonus-myoclonus ataxia (POMA). We report here six individuals with de novo frameshift variants in the NOVA2 gene affected with a severe neurodevelopmental disorder characterized by intellectual disability (ID), motor and speech delay, autistic features, hypotonia, feeding difficulties, spasticity or ataxic gait and abnormal brain MRI. The six variants lead to the same reading frame, adding a common 133 aa long proline rich C-terminus part instead of the last KH RNA binding domain. We detected forty-one genes differentially spliced after NOVA2 inactivation in human neural cells. The mutant NOVA2 protein shows decreased ability to bind a target RNA, to regulate specific splicing events and to rescue the phenotype of altered retinotectal axonal pathfinding induced by loss of NOVA2 ortholog in zebrafish. Our results suggest a partial loss-of-function mechanism rather than a full heterozygous loss of function, although a specific contribution of the novel C terminal extension cannot be excluded on the basis of the genetic findings.

genetics↗