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Updated: Sep 20, 2025
Array Comparative Genomic Hybridization Array CGH for Detection of Genomic Copy Number Variants
Published on: February 21, 2015
Targeted copy number variant identification across the neurodegenerative disease spectrum
Allison A Dilliott1, Kristina K Zhang2, Jian Wang3
1Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, Quebec, Canada.
Background:
Although genetic factors are known to contribute to neurodegenerative disease susceptibility, there remains a large amount of heritability unaccounted for across the diagnoses. Copy number variants (CNVs) contribute to these phenotypes, but their presence and influence on disease state remains relatively understudied.
Methods:
Here, we applied a depth of coverage approach to detect CNVs in 80 genes previously associated with neurodegenerative disease within participants of the Ontario Neurodegenerative Disease Research Initiative (n = 519).
Results:
In total, we identified and validated four CNVs in the cohort, including: (1) a heterozygous deletion of exon 5 in OPTN in an Alzheimer's disease participant; (2) a duplication of exons 1-5 in PARK7 in an amyotrophic lateral sclerosis participant; (3) a duplication of >3 Mb, which encompassed ABCC6, in a cerebrovascular disease (CVD) participant; and (4) a duplication of exons 7-11 in SAMHD1 in a mild cognitive impairment participant. We also identified 43 additional CNVs that may be candidates for future replication studies.
Conclusion:
The identification of the CNVs suggests a portion of the apparent missing heritability of the phenotypes may be due to these structural variants, and their assessment is imperative for a thorough understanding of the genetic spectrum of neurodegeneration.
