Mutation In SOD1 And Genome Polymorphism In SALS

Amyotrophic lateral sclerosis(ALS) is a progressive paralytic disorder resulting from the degeneration of motor neurons in the brain and spinal cord.Sporadic ALS(SALS) accounts for the majority of patients.Copper/zinc superoxide dismutase 1(SOD1) gene mutations are responsible for 1~7%of apparent SALS cases.There were several SNPs reported be associated with SALS in recently published articles about whole-Genome analysis of SALS.OBJECTIVE:We search for novel SOD1 mutations in SALS cases colleted from 2007 to 2008;study the genome polymorphism in SALS of chinese origin.METHODS:We extracted the genomic DNA from the leukocytes of whole blood samples,amplicated the 5 exon of SOD1 gene,finished the mutation sanning using th HRM method,sequenced the variant PCR product.Processed the asymmetric PCR in the presence of an unlabeled probe that contain the target SNP locus,genotyped the product on LightScanner.RESULTS:1.In 1 out of 19 SALS patients we found a novel missense mutation SOD1 V47A in exon 2.2.We figured out a varitant on SOD1 8227 base,proved as a SNP.3.We genotyped two SNP,rs6700125 and rs10260404,that was reported consistently strongly associated with susceptibility to SALS in different populations of European and American ancestry.The rs6700125(x~2=0.176,OR=1.12,95%CI:0.67-1.87) and rs10260404(x~2=0.292,OR=1.26,95%CI:0.55-2.87) were not strongly associated with ALS in Chinese people. CONCLUSIONS:1.The SOD1 V47A mutation we found has the quite different phenotype compared with the same allele locus mutation reported,V47F; SOD1 A8227C we figured is proved as a SNP;Now,we have identified 6 novel mutations in 130 SALS patients and 2 FALS families since 2006.2.The rs6700125 and rs10260404 are both not the SNP associated with SALS of the Chinese ancestry.