Segmental copy-number gain within the region of isopentenyl diphosphate isomerase genes in sporadic amyotrophic lateral sclerosis

Autor: Kenichi Matsubara, Mitsuru Emi, Toru Kawanami, Fumiaki Tanaka, Itaru Toyoshima, Hidenori Sato, Kenji Tsuburaya, Tadashi Katagiri, Manabu Wada, Gen Sobue, Takeo Kato, Shigeki Arawaka
Rok vydání: 2010
Předmět:
Zdroj: Biochemical and Biophysical Research Communications. 402:438-442
ISSN: 0006-291X
DOI: 10.1016/j.bbrc.2010.10.056
Popis: Aims: Sporadic amyotrophic lateral sclerosis (SALS) seems to be a multifactorial disease, the pathogenesis of which may involve both genetic and environmental factors. The present study aims at identifying a possible genetic change that confers risk for SALS. Methods: We performed whole-genome screening of a copy-number variation (CNV) using a CNV beadchip, followed by real-time quantitative polymerase chain reaction (qPCR) and region-targeted high-density oligonucleotide tiling microarray. Results: Within the 40-kb region on 10p15.3 subtelomere, which harbours two genes encoding isopentenyl diphosphate isomerase 1 (IDI1) and IDI2, we found a segmental copy-number gain in a large proportion of SALS patients. qPCR analysis demonstrated the copy-number gain in 46 out of 83 SALS patients, as compared with 10 out of 99 controls (p = 4.86 × 10−11, Odds Ratio 10.8); subsequent tiling microarray validated qPCR results and elucidated the fine structure of segmental gains. Conclusions: A segmental copy-number gain in the IDI1/IDI2 gene region may play a significant role in the pathogenesis of SALS.
Databáze: OpenAIRE
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