Introduction Several disorders have been associated with genetic variants. Copy number variations (CNVs) are documented micro DNA insertions and deletions that may be ten times more frequent than point mutations. We undertook a genome-wide scan to find CNVs associated with adolescent idiopathic scoliosis (AIS).
Methods 879 white individuals with AIS severe spine curvatures and 1486 white controls were evaluated for CNVs with the Affymetrix 6.0 HUSNP array. After implementation of quality filters, data were quantile normalised. Copy number analysis was done with Helix Tree (Golden Helix, Bozeman, MT, USA). The copy number segments were measured with the Golden Helix's univariate segmentation algorithm. Statistically different segments were extracted with mean Log2 ratio intensity for that segment to highlight deletions, neutrals, and duplications. We then undertook association analysis on those segments. A p value of less than 10–7 was regarded as significant.
Results We recorded 143 significant segments or regions associated with AIS. 94 of these regions showed gains of copy whereas 49 had deletions. 63 of these significant regions map to known genes. Biological functions of the proteins coded by the genes identified complex groups associated with embryonic development, nervous system development and function, and bone and soft tissue development. These groups present an extensive overlap with the biological function groups that were generated with associated single-nucleotide polymorphism data from the same group of individuals.
Conclusions For the first time we show significant copy number loss or gain in several genomic regions for patients with AIS with severe spine curves compared with a control population. We are testing CNVs in patients with a mild spine curvature to establish whether they improve the performance of AIS prognostic testing. The identification of novel or rare CNVs in severe cases of AIS could lead to the enhancement of prognostic testing and help to identify specific biological pathways that cause AIS or accelerate AIS progression.
- Copyright © 2011, British Editorial Society of Bone & Joint Surgery