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.
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 SALSpatients. qPCR analysis demonstrated the copy-number gain in 46 out of 83 SALSpatients, 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.
Authors: Fedik Rahimov; Oliver D King; Doris G Leung; Genila M Bibat; Charles P Emerson; Louis M Kunkel; Kathryn R Wagner Journal: Proc Natl Acad Sci U S A Date: 2012-09-17 Impact factor: 11.205
Authors: T Sekimoto; M Ishii; M Emi; S Kurogi; T Funamoto; Y Yonezawa; T Tajima; T Sakamoto; H Hamada; E Chosa Journal: Bone Joint Res Date: 2017-07 Impact factor: 5.853