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Published on: July 16, 2021
Homozygosity analysis in amyotrophic lateral sclerosis
Kin Mok1, Hannu Laaksovirta, Pentti J Tienari
1Reta Lila Weston Research Laboratories, Department of Molecular Neuroscience, and Department of Clinical Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
European Journal of Human Genetics : EJHG
|April 25, 2013
Summary
This study investigated rare recessive genetic mutations in Amyotrophic Lateral Sclerosis (ALS). Findings suggest increased homozygosity in ALS patients, pointing to potential new genetic causes for the disease.
Area of Science:
- Genetics
- Neurology
- Genomics
Background:
- Amyotrophic Lateral Sclerosis (ALS) presents as familial or sporadic, with some cases showing dominant or recessive inheritance patterns.
- Sporadic ALS may stem from rare homozygous recessive mutations, necessitating further genetic investigation.
Purpose of the Study:
- To identify potential recessive genetic variants contributing to Amyotrophic Lateral Sclerosis (ALS) through homozygosity analysis.
- To analyze genome-wide association study (GWAS) data for homozygosity patterns in ALS patients and controls.
Main Methods:
- Examined homozygosity segments in UK patients (620 ALS, 5169 controls) and a multinational pooled cohort (2017 ALS, 6918 controls).
- Utilized GWAS data to identify and filter rare homozygous segments across the genome.
- Performed statistical analyses to compare homozygosity patterns between ALS cases and controls.
Main Results:
- ALS patients exhibited significantly longer total autosomal genome homozygosity segments compared to controls (P=0.05).
- Pooled analysis revealed more homozygosity regions, higher prevalence, longer segments, greater genome coverage, and increased overlap with RefSeq genes in ALS cases (P < 1x10(-5)).
- Significant associations were identified in three chromosomal regions, including the SOD1 region on chromosome 21, and regions on chromosomes 1 and 5, implicating over twenty potential genes.
Conclusions:
- The findings indicate the presence of rare recessive genetic factors contributing to ALS.
- These identified genetic factors are not typically detected as common variants in GWAS.
- This research opens avenues for discovering novel recessive genetic causes of ALS.
