Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease.

Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease.

Nature (1995-06-29)

R Sherrington, E I Rogaev, Y Liang, E A Rogaeva, G Levesque, M Ikeda, H Chi, C Lin, G Li, K Holman, T Tsuda, L Mar, J F Foncin, A C Bruni, M P Montesi, S Sorbi, I Rainero, L Pinessi, L Nee, I Chumakov, D Pollen, A Brookes, P Sanseau, R J Polinsky, W Wasco, H A Da Silva, J L Haines, M A Perkicak-Vance, R E Tanzi, A D Roses, P E Fraser, J M Rommens, P H St George-Hyslop

PMID7596406

摘要

Some cases of Alzheimer's disease are inherited as an autosomal dominant trait. Genetic linkage studies have mapped a locus (AD3) associated with susceptibility to a very aggressive form of Alzheimer's disease to chromosome 14q24.3. We have defined a minimal cosegregating region containing the AD3 gene, and isolated at least 19 different transcripts encoded within this region. One of these transcripts (S182) corresponds to a novel gene whose product is predicted to contain multiple transmembrane domains and resembles an integral membrane protein. Five different missense mutations have been found that cosegregate with early-onset familial Alzheimer's disease. Because these changes occurred in conserved domains of this gene, and are not present in normal controls, they are likely to be causative of AD3.