Isoform-Specific Variant and Expression Analysis of Epigenetic Genes in Neurodevelopment and Disease
type: CreativeWork
description: Isoform-Specific Genetic Analysis of Epigenetic Machinery Genes in Neurodevelopment and Disease Úlfur Benedikt Fjölnisson¹, Katrín Möller¹, Hans Tómas Björnsson¹,²,³ ¹ Department of Medicine, University of Iceland, Reykjavík, Iceland ² Johns Hopkins University, Baltimore, USA ³ University Hospital, Reykjavík, Iceland Introduction Missense mutations in epigenetic machinery (EM) genes are frequently associated with neurodevelopmental disorders. Studying the isoform-specific distribution of pathogenic variants and the timing of isoform expression may reveal critical mechanisms underlying these diseases. Aims To assess whether pathogenic missense variants are enriched in regions unique to non-canonical isoforms and whether these isoforms show stage-specific expression during neurodevelopment. Methods Public databases (ClinVar, gnomAD, Ensembl BioMart) were used to compute missense variant densities in non-overlapping, isoform-specific exons of EM genes. Genome-wide variant data were used to ensure sufficient coverage. Enrichment was tested using Fisher’s exact test with FDR correction. Isoform expression patterns across stages of mouse neurodevelopment were analyzed using ANOVA and Tukey’s HSD. A composite score integrating expression and variant burden was applied to prioritize candidate genes. Results Several non-canonical isoforms demonstrated significant enrichment for pathogenic variants and dynamic expression changes during neurodevelopment. One gene in particular showed both statistical and biological relevance, making it a strong candidate for future study. Conclusion This study supports the importance of transcript-aware variant interpretation and highlights the potential for discovering novel disease mechanisms through isoform-specific analysis in neurodevelopmental disorders.
abstract: Isoform-Specific Genetic Analysis of Epigenetic Machinery Genes in Neurodevelopment and Disease Úlfur Benedikt Fjölnisson¹, Katrín Möller¹, Hans Tómas Björnsson¹,²,³ ¹ Department of Medicine, University of Iceland, Reykjavík, Iceland ² Johns Hopkins University, Baltimore, USA ³ University Hospital, Reykjavík, Iceland Introduction Missense mutations in epigenetic machinery (EM) genes are frequently associated with neurodevelopmental disorders. Studying the isoform-specific distribution of pathogenic variants and the timing of isoform expression may reveal critical mechanisms underlying these diseases. Aims To assess whether pathogenic missense variants are enriched in regions unique to non-canonical isoforms and whether these isoforms show stage-specific expression during neurodevelopment. Methods Public databases (ClinVar, gnomAD, Ensembl BioMart) were used to compute missense variant densities in non-overlapping, isoform-specific exons of EM genes. Genome-wide variant data were used to ensure sufficient coverage. Enrichment was tested using Fisher’s exact test with FDR correction. Isoform expression patterns across stages of mouse neurodevelopment were analyzed using ANOVA and Tukey’s HSD. A composite score integrating expression and variant burden was applied to prioritize candidate genes. Results Several non-canonical isoforms demonstrated significant enrichment for pathogenic variants and dynamic expression changes during neurodevelopment. One gene in particular showed both statistical and biological relevance, making it a strong candidate for future study. Conclusion This study supports the importance of transcript-aware variant interpretation and highlights the potential for discovering novel disease mechanisms through isoform-specific analysis in neurodevelopmental disorders.
author: Úlfur Benedikt Fjölnisson 2003-
language: en
keywords: Læknisfræði, Stökkbreytingar, Taugaþroskaraskanir, Erfðabreytingar
date published: 2025-05-20T13:28:05Z
date modified: 2026-07-27T21:39:44Z
provider: University of Iceland
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Iceland

PropertyValue
property ID: Handle
value: https://hdl.handle.net/1946/50267