Genetic Predisposition in Degenerative Lumbar Scoliosis due to the Copy Number Variation

STUDY DESIGN: Comparative genomic hybridization (CGH) microarrays. OBJECTIVE: To identify genomic copy number variations (CNVs) in degenerative lumbar scoliosis (DLS) patients, and investigate the possibility of genetic predisposition in DLS. SUMMARY OF BACKGROUND DATA: Genome scanning technology enables search for presence of CNVs. CGH microarray is a useful procedure in a genome-wide study. METHODS: Among 45 consecutive patients who were diagnosed as DLS, 15 patients who manifested greatest Cobb's angle were selected for the array-CGH based CNV analysis. Control group was blood samples from 58 individuals without DLS. Oligonucleotide CGH microarray was utilized to analyze the CNV. Gene searches were performed for CNV DNA with significant gene-dosage difference. Validation qualitative PCR(qPCR) was performed at 3 genetic loci: at chromosome 2--TMEM163 gene, at chromosome 16--ANKRD 11 gene, and at chromosome 18--NFATC1 gene. RESULTS: Genomic gains and losses were observed using the oligonucleotide CGH microarray. Identified CNVs were 446 ± 129 per individual. Gain- and loss-CNVs were identified as 196 ± 24 and 250 ± 110, respectively. The length of total CNV per individual was 30,946,730 ± 31,658,175 bp, and mean CNV-length was 61,017 ± 40,620 (median length 6411 ± 1994). Comparison with control group revealed 260 CNVs, which were significant (P < 10(-3)). Validation qPCR for gene-dosage comparison of DLS group DNA versus control group DNA in TMEM163 (P < 0.001); ANKRD 11 (P = 0.000); and NFATC1 (P = 0.000) gene showed significant difference. CONCLUSION: Various whole-genome CNVs specific to DLS patients were observed. Validation qPCR confirmed significantly different gene-dosages for TMEM163, ANKRD 11, and NFATC1 genes. We consider that the expression of DLS is supported by various typical CNV-associated structural variants of the genome.