Segmental copy-number gain within the region of isopentenyl diphosphate isomerase genes in sporadic amyotrophic lateral sclerosis.
OBJECTIVE
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.
Kato
Takeo
T
Department of Neurology, Haematology, Metabolism, Endocrinology, and Diabetology, Yamagata University Faculty of Medicine, Yamagata, Japan. tkato@med.id.yamagata-u.ac.jp
Emi
Mitsuru
M
Sato
Hidenori
H
Arawaka
Shigeki
S
Wada
Manabu
M
Kawanami
Toru
T
Katagiri
Tadashi
T
Tsuburaya
Kenji
K
Toyoshima
Itaru
I
Tanaka
Fumiaki
F
Sobue
Gen
G
Matsubara
Kenichi
K
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D019748:Carbon-Carbon Double Bond Isomerases / Q000235:genetics*; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D018628:Gene Dosage; D045782:Hemiterpenes; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D016615:Telomere / Q000235:genetics
D045782:Hemiterpenes; D019748:Carbon-Carbon Double Bond Isomerases; C021453:isopentenyldiphosphate delta-isomerase