Repetitive Sequences in Neurological Diseases and Health*
Date: October 18, 2026
Time: 10:00 am to 11:30 am
Room: Pacific Jewel Ballroom
Track: Plenary
Session Description
More than 50% of the human genome consists of repetitive DNA, including micro- and macrosatellite repeats that contribute to a range of neurological diseases. This session will highlight recent advances in the biology of repeat expansion disorders, with a focus on somatic repeat instability as a key driver of disease and a potential therapeutic target.
Faculty will also examine emerging data on the unexpectedly high prevalence of microsatellite expansions in the general population and the implications for disease risk. In addition, the session will explore epigenetic and molecular mechanisms underlying facioscapulohumeral muscular dystrophy, including the role of D4Z4 repeat contractions.
Together, these presentations will provide a comprehensive overview of evolving concepts in repeat biology and their relevance to disease pathogenesis and therapeutic development.
Learning Objectives
At the conclusion of this session, attendees will be able to:
- Analyze the contribution of repeat expansion and contraction disorders to both rare and common neurological diseases, including factors leading to underdiagnosis.
- Evaluate the limitations of conventional genetic testing and apply specialized diagnostic strategies to detect repeat expansion and contraction mutations.
- Assess the clinical, therapeutic, and familial implications of accurate diagnosis, including impact on emerging treatment strategies and genetic counseling.
Speakers
- (Chair) Laura Ranum, PhD, FANA
- (Co-Chair, Speaker) Silvère Van der Maarel, PhD
- (Speaker) Steven McCarroll, PhD
- (Speaker) Arianna Tucci, MD, PhD
- (Awardee) David Newman-Toker, MD, PhD
- (Awardee) Neil Shneider, MD, PhD, FANA
The Ticking DNA Clock: Lifelong Somatic Expansion of DNA Repeats and the Pathogenesis of Huntington's Disease
Description
In this presentation, Dr. McCarroll will review how inherited DNA-repeat disorders such as Huntington’s Disease (HD) have long challenged our understanding: Why do patients have decades of good health before symptoms commence? Why do such disorders devastate some types of neurons but not others? Describing experiments that reveal a surprising dynamic. The inherited DNA repeat that causes HD undergoes decades of somatic expansion in the vulnerable neurons, expanding several times its inherited length before becoming toxic.
Understanding Repeat Expansion Diseases Using Population-scale Genomic Data
Description
In this presentation, Dr. Tucci will discuss how DNA repeat expansions are a major cause of neurological disease but have been difficult to detect using short-read sequencing. Using large-scale genomic data, we developed methods now implemented in the National Health Service to accurately detect these repeats. Analyzing >500,000 individuals, we show they are 2-3 times more common than recognized, and quantified mutations in families. This work reframes these disorders as a continuum and enables improved risk prediction.
D4Z4 Macrosatellite Repeat Rearrangements in Facioscapulohumeral Muscular Dystrophy
Description
In this presentation, Dr. Van Der Maarel will discuss repetitive DNA that is often overlooked in genomic studies. Macrosatellite repeats, tandem arrays of ≥500 bp units, are poorly characterized. Facioscapulohumeral dystrophy (FSHD) is caused by epigenetic dysregulation of the D4Z4 macrosatellite, resulting in derepression of DUX4 in skeletal muscle. This overview addresses the genetic and epigenetic basis of DUX4 expression, global variation and modifiers of the FSHD locus, downstream pathogenic effects, and current therapeutic strategies.
Awardee Remarks
