title: Cloning of a gene bearing missense mutations in early onset familial Alzheimer's disease: a Calabrian study.
abstract: Alzheimer's disease (AD) is a common and serious disease whose incidence increases with age affecting millions of people. While the aetiology of sporadic AD cases remains obscure, considerable progress has been made in the isolation and cloning of genes causing familial AD (FAD). The problem of gene identification and isolation has been solved for chromosome 14 through the study of large, homogeneous pedigrees, like FAD Calabrian kindreds, which, having been the subject of extensive genealogical study, have a well-known clinical and genetic identity. Several independent families (N, To, C, and FJ01) affected with early onset FAD were studied in Calabria (Southern Italy). A genealogical "blanket" method has allowed these families to merge into two larger kindreds. Identical phenotypes and neighbouring places of origin suggested a common founder. Even though genealogical reconstruction failed to identify the common ancestor, inspection of the haplotype data showed that a common extended haplotype was shared by these kindreds. AD3 gene has been isolated and cloned in BCE sequence. Met 146 Leu mutation in these kindreds is indeed identical by descent.
authors.affiliation: Regional Neurogenetics Centre, Terme, Italy.
authors.forename: A C
authors.initials: AC
authors.lastname: Bruni
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics*; D001118:Argentina; D001499:Bayes Theorem; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D005260:Female; D005789:Genealogy and Heraldry; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D005826:Genetics, Medical / Q000379:methods; D006239:Haplotypes; D006801:Humans; D007558:Italy / Q000208:ethnology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D053764:Presenilin-1
chemical_list: D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1