Whole genome sequencing analysis reveals post-zygotic mutation variability in monozygotic twins discordant for amyotrophic lateral sclerosis.
Neurobiol Aging
; 122: 76-87, 2023 02.
Article
en En
| MEDLINE
| ID: mdl-36521271
ABSTRACT
Amyotrophic lateral sclerosis is a heterogeneous, fatal neurodegenerative disease, characterized by motor neuron loss and in 50% of cases also by cognitive and/or behavioral changes. Mendelian forms of ALS comprise approximately 10-15% of cases. The majority is however considered sporadic, but also with a high contribution of genetic risk factors. To explore the contribution of somatic mutations and/or epigenetic changes to disease risk, we performed whole genome sequencing and methylation analyses using samples from multiple tissues on a cohort of 26 monozygotic twins discordant for ALS, followed by in-depth validation and replication experiments. The results of these analyses implicate several mechanisms in ALS pathophysiology, which include a role for de novo mutations, defects in DNA damage repair and accelerated aging.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Enfermedades Neurodegenerativas
/
Esclerosis Amiotrófica Lateral
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Neurobiol Aging
Año:
2023
Tipo del documento:
Article
País de afiliación:
Países Bajos