Rare diseases of epigenetic origin: Challenges and opportunities

Frontiers in Genetics

Genetics

Mehul Sharma¹  Stuart E. Turvey¹  William T. Gibson²  Michael S. Kobor³  Maggie P. Fu³  Sarah M. Merrill³ 

[1] BC Children’s Hospital Research Institute, Vancouver, BC, Canada;Department of Pediatrics, Faculty of Medicine, BC Children’s Hospital, University of British Columbia, Vancouver, BC, Canada;Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada;BC Children’s Hospital Research Institute, Vancouver, BC, Canada;Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada;Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada;BC Children’s Hospital Research Institute, Vancouver, BC, Canada;

关键词: epigenetics;    rare disease;    bioinformatics analysis;    DNA methylation;    histone modification;    chromatin remodeler;   

DOI  :  10.3389/fgene.2023.1113086

 received in 2022-12-01, accepted in 2023-01-24,  发布年份 2023

来源: Frontiers

【 摘 要 】

Rare diseases (RDs), more than 80% of which have a genetic origin, collectively affect approximately 350 million people worldwide. Progress in next-generation sequencing technology has both greatly accelerated the pace of discovery of novel RDs and provided more accurate means for their diagnosis. RDs that are driven by altered epigenetic regulation with an underlying genetic basis are referred to as rare diseases of epigenetic origin (RDEOs). These diseases pose unique challenges in research, as they often show complex genetic and clinical heterogeneity arising from unknown gene–disease mechanisms. Furthermore, multiple other factors, including cell type and developmental time point, can confound attempts to deconvolute the pathophysiology of these disorders. These challenges are further exacerbated by factors that contribute to epigenetic variability and the difficulty of collecting sufficient participant numbers in human studies. However, new molecular and bioinformatics techniques will provide insight into how these disorders manifest over time. This review highlights recent studies addressing these challenges with innovative solutions. Further research will elucidate the mechanisms of action underlying unique RDEOs and facilitate the discovery of treatments and diagnostic biomarkers for screening, thereby improving health trajectories and clinical outcomes of affected patients.

【 授权许可】

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Copyright © 2023 Fu, Merrill, Sharma, Gibson, Turvey and Kobor.