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).

Purpose: Adolescent idiopathic scoliosis (AIS) is know to occur in families and research has shown that in populations or predominantly Northern European origin, 97% of AIS patients are related to families with AIS. It affects 1–2% of the population and results in deformities treated by bracing and surgery. Brace prescription is empirical and surgery is reserved for late cases and brace failures. Identifying the genetic markers for AIS would allow creation of a diagnostic gene-based test that may also have prognostic value for differentiating progressive and non-progressive curves.

Methods: A 21 million name data base of the original European pioneers in Utah was assembled including 3 million descendents and 18 million ancestors. 500 DNA samples from affected and first degree unaffected relatives were collected and genotypes determined with capillary electrophoresis using 763 autosomal markers and gene chip scanning for 116 000 SNPs. Disease haplotypes were also scanned with a 500K SNP chip to further narrow the position of each loci.

Results: Two markers were identified with LOD scores of 7.0 and 7.3. p-values from SNP scanning were highly significant. More detailed descriptions of these genotypes will be presented.

Conclusion: Two genetic markers were identified, one of which was present in 95% of patients with AIS greater than 40°. In our population, no one with AIS less than 40° had these markers. A genotype test for AIS may be possible that would offer both diagnostic and prognostic value. Further characterization of the genes and their mutations could give information concerning the molecular pathway that lead to disease expression.