Podium Presentation Abstracts
Summary: Copy number variations (CNVs) are small DNA insertions and deletions that may be ten times more frequent and more likely to cause disease than point mutations. For the first time, we show significant copy number loss or gain in several genomic regions associated with severe AIS. The molecular pathways implicated overlap with the biological functions implicated by genome‐wide association data from the same set of individuals.
Introduction: Developmental disorders are often associated with genetic variants. Copy number variations (CNVs) are recently documented micro DNA insertions and deletions that may be ten times more frequent than point mutations. CNVs may be more likely to cause disease than point mutations.
Methods: We performed a genome‐wide scan to find CNVs associated with Adolescent Idiopathic Scoliosis (AIS). A total of 879 Caucasian individuals with severe AIS and 1486 Caucasian controls were evaluated for CNVs using the Affymetrix 6.0 HuSNP array. After the implementation of quality filters the data were quantile and normalized. Copy number analysis were determined using Helix Tree (Golden Helix, Bozeman, MT). The copy number segments were determined using the Golden Helix's Univariate Segmentation Algorithm. Statistically different segments were extracted using mean Log2 ration intensity for that segment to highlight deletions, neutrals and duplications. We then performed association analysis on those segments. A p‐value of <10‐7 was considered evidence of significance.
Results: We found 143 significant segments/regions associated with AIS. Ninety‐four of those regions showed gains of copy while 49 had deletions. Sixty‐three of these significant regions map to known genes. Biological functions of these genes identified reveal complex groups associated to embryonic development, nervous system development and function, and tissue development.
Conclusion: The molecular pathways implicated overlap with the biological functions using genome‐wide association (SNP) data from the same set of individuals. For the first time we show significant copy number loss or gain in several genomic regions associated with severe AIS.
Significance: The identification of CNVs in severe AIS could not only lead to the enhancement of prognostic testing in AIS, but could also help us identify specific biological pathways that cause AIS or accelerate AIS progression.