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Updated: May 9, 2026
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Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
Delineating the genetic heterogeneity of ALS using targeted high-throughput sequencing
Kevin P Kenna1, Russell L McLaughlin, Susan Byrne
1Smurfit Institute of Genetics, Trinity College, Dublin, Ireland.
Journal of Medical Genetics
|July 25, 2013
Summary
Genetic analysis revealed that up to 17% of Irish amyotrophic lateral sclerosis (ALS) patients carry high-penetrance variants. The genetic landscape of ALS in Ireland significantly differs from other European populations, highlighting the importance of regional genetic studies.
Area of Science:
- Genetics
- Neurology
- Molecular Biology
Background:
- Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease.
- Over 100 genes are implicated in ALS aetiology.
- Understanding genetic contributions is crucial for clinical and research efforts.
Purpose of the Study:
- To characterize genetic variation in ALS.
- To investigate Mendelian and low-penetrance genes in an Irish ALS cohort.
- To compare Irish ALS genetic profiles with other European populations.
Main Methods:
- Targeted high-throughput sequencing of 33 ALS-associated genes.
- Analysis of 444 Irish ALS cases and 311 controls.
- Comparison of variant frequencies across populations.
Main Results:
- High-penetrance ALS variants found in 17.1% of patients (38% of familial ALS, 14.5% of sporadic ALS).
- Specific gene variant frequencies identified, including C9orf72 (8.78%), SETX (2.48%), and others.
- Significant differences in disease variation spectrum compared to other European populations (p=1.7×10⁻⁴).
Conclusions:
- Up to 17% of Irish ALS cases harbor high-penetrance variants.
- Genetic susceptibility in Ireland is distinct from other European cohorts.
- Concomitant analysis of multiple disease genes may be important for understanding ALS aetiology.
