Human CCS gene: genomic organization and exclusion as a candidate for amyotrophic lateral sclerosis (ALS).
BACKGROUND
Amyotrophic lateral sclerosis (ALS) is a progressive lethal disorder of large motor neurons of the spinal cord and brain. In approximately 20% of the familial and 2% of sporadic cases the disease is due to a defect in the gene encoding the cytosolic antioxidant enzyme Cu, Zn-superoxide dismutase (SOD1). The underlying molecular defect is known only in a very small portion of the remaining cases and therefore involvement of other genes is likely. As SOD1 receives copper, essential for its normal function, by the copper chaperone, CCS (Copper Chaperone for SOD), we considered CCS as a potential candidate gene for ALS.


RESULTS
We have characterized the genomic organization of CCS and determined exon-intron boundaries. The 823 bp coding region of the CCS is organized in 8 exons. We have evaluated involvement of the CCS in ALS by sequencing the entire coding region for mutations in 20 sporadic ALS patients.


CONCLUSIONS
No causative mutations for the ALS have been detected in the CCS gene in 20 sporadic ALS patients analyzed, but an intragenic single nucleotide polymorphism has been identified.
Silahtaroglu
Asli N
AN
Wilhelm Johannsen Centre for Functional Genome Research, Department of Medical Genetics, IMBG, The Panum Institute, University of Copenhagen, Copenhagen, Denmark. asli@medgen.ku.dk
Brondum-Nielsen
Karen
K
Gredal
Ole
O
Werdelin
Lene
L
Panas
Marios
M
Petersen
Michael B
MB
Tommerup
Niels
N
Tümer
Zeynep
Z
D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods*; D015331:Cohort Studies; D004252:DNA Mutational Analysis / Q000379:methods; D030541:Databases, Genetic; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
C114678:CCS protein, human; D018832:Molecular Chaperones