DNA methylome, R-loop and clinical exome profiling of patients with sporadic amyotrophic lateral sclerosis

作者：Orsolya Feró, Dóra Varga, Éva Nagy, Zsolt Karányi, Éva Sipos, József I. Engelhardt, Nóra Török, István Balogh, Borbála Vető, István Likó, Ábel Fóthi, Z. Szabó, Gábor Halmos, László Vécsei, Tamás Arányi, Lóránt Székvölgyi · 发表于：Scientific Data · 年份：2024 · DOI：10.1038/s41597-024-02985-y · 被引用次数：8 · 研究领域：Amyotrophic Lateral Sclerosis Research、Neurogenetic and Muscular Disorders Research

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the death of motor neurons, the aetiology of which is essentially unknown. Here, we present an integrative epigenomic study in blood samples from seven clinically characterised sporadic ALS patients to elucidate molecular factors associated with the disease. We used clinical exome sequencing (CES) to study DNA variants, DNA-RNA hybrid immunoprecipitation sequencing (DRIP-seq) to assess R-loop distribution, and reduced representation bisulfite sequencing (RRBS) to examine DNA methylation changes. The above datasets were combined to create a comprehensive repository of genetic and epigenetic changes associated with the ALS cases studied. This repository is well-suited to unveil new correlations within individual patients and across the entire patient cohort. The molecular attributes described here are expected to guide further mechanistic studies on ALS, shedding light on the underlying genetic causes and facilitating the development of new epigenetic therapies to combat this life-threatening disease.