Whole genome sequencing analysis reveals post-zygotic mutation variability in monozygotic twins discordant for amyotrophic lateral sclerosis.

Publikation

Whole genome sequencing analysis reveals post-zygotic mutation variability in monozygotic twins discordant for amyotrophic lateral sclerosis.

Wissenschaftlicher Artikel/Review - 17.11.2022

Tazelaar Gijs H P, Hop Paul J, Seelen Meinie, Van Vugt Joke J F A, van Rheenen Wouter, Kool Lindy, van Eijk Kristel R, Gijzen Marleen, Dooijes Dennis, Moisse Matthieu, Calvo Andrea, Moglia Cristina, Brunetti Maura, Canosa Antonio, Nordin Angelica, Pardina Jesus S Mora, Ravits John, Al-Chalabi Ammar, Chio Adriano, McLaughlin Russell L, Hardiman Orla, Van Damme Philip, de Carvalho Mamede, Neuwirth Christoph, Weber Markus, Andersen Peter M, van den Berg Leonard H, Veldink Jan H, van Es Michael A

Zitation

Tazelaar G, Hop P, Seelen M, Van Vugt J, van Rheenen W, Kool L, van Eijk K, Gijzen M, Dooijes D, Moisse M, Calvo A, Moglia C, Brunetti M, Canosa A, Nordin A, Pardina J, Ravits J, Al-Chalabi A, Chio A, McLaughlin R, Hardiman O, Van Damme P, de Carvalho M, Neuwirth C, Weber M, Andersen P, van den Berg L, Veldink J, van Es M. Whole genome sequencing analysis reveals post-zygotic mutation variability in monozygotic twins discordant for amyotrophic lateral sclerosis. Neurobiol Aging 2022; 122:76-87.

Art

Wissenschaftlicher Artikel/Review (Englisch)

Zeitschrift

Neurobiol Aging 2022; 122

Veröffentlichungsdatum

17.11.2022

eISSN (Online)

1558-1497

Seiten

76-87

Kurzbeschreibung/Zielsetzung

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.