ABSTRACT Sporadic amyotrophic lateral sclerosis (SALS) is regarded as a multifactorial disease; both genetic and environmental factors may contribute to the pathogenesis of SALS. To identify a possible genetic change that confers risk for SALS, we conducted whole-genome screening of a copy-number variation (CNV) with a CNV beadchip and a high-density oligonucleotide tiling microarray, followed by real-time quantitative polymerase chain reaction (qPCR). In the 1.1- to 5.5- kb region within the gene encoding the proprotein convertase subtilisin/kexin type 6 (PCSK6) on the chromosome 15q26.3 subtelomere, we found a copy-number loss in a large proportion (8 of 11; 72%) of SALS patients. Subsequent tiling microarray validated the results and revealed the fine structure of segmental loss. qPCR analysis confirmed the copy-number loss in 13 out of 23 SALS patients, as compared with 7 out of 44 controls (p = 0.0015, Odds Ratio: 6.63, 95% CI: 1.89-25.72). The present study suggests that a segmental copy-number loss of the PCSK6 gene may play a role in the pathogenesis of SALS.
View Full Article
|