Familial Alzheimer's disease in kindreds with missense mutations in agene on chromosome 1 related to the Alzheimer's disease type 3 gene

来自 Semantic Scholar

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作者：

EI Rogaev，R Sherrington，EA Rogaeva，G Levesque，M Ikeda，Y Liang，H Chi，C Lin，K Holman，T Tsuda

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摘要：

We report the cloning of a novel gene (E5-1) encoded on chromosome 1 which has substantial nucleotide and amino-acid sequence similarity to the S182 gene on chromosome 14q24.3. Mutations, including three new missense mutations in the S182 gene, are associated with the AD3 subtype of early-onset familial Alzheimer's disease (AD). Both the E5-1 and the S182 proteins are predicted to be integral membrane proteins with seven membrane-spanning domains, and a large exposed loop between the sixth and seventh transmembrane domains. Analysis of the nucleotide sequence of the open reading frame (ORF) of the E5-1 gene led to the discovery of two missense substitutions at conserved amino-acid residues in affected members of pedigrees with a form of familial AD that has a later age of onset than the AD3 subtype (50-70 years versus 30-60 years for AD3). These observations imply that the E5-1 gene on chromosome 1 and the S182 gene on chromosome 14q24.3 are members of a family of genes (presenilins) with related functions, and indicates that mutations in conserved residues of E5-1 could also play a role in the genesis of AD. Our results also indicate that still other AD susceptibility genes exist.

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关键词：

Alzheimer Disease genetics Chromosomes Human Pair 1 Membrane Proteins 染色体人 1对膜蛋白质类突变