Cloning of a Gene Bearing Missense Mutations in Early-Onset Familial Alzheimer's Disease

Nature. 1995 Jun 29;375(6534):754-60. doi: 10.1038/375754a0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Human, Pair 14*
  • Cloning, Molecular*
  • Female
  • Humans
  • Male
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics*
  • Mice
  • Molecular Sequence Data
  • Mutation*
  • Open Reading Frames
  • Pedigree
  • Presenilin-1
  • Protein Structure, Secondary
  • Transcription, Genetic

Substances

  • Membrane Proteins
  • PSEN1 protein, human
  • Presenilin-1

Associated data

  • GENBANK/L40391
  • GENBANK/L40392
  • GENBANK/L40393
  • GENBANK/L40394
  • GENBANK/L40395
  • GENBANK/L40396
  • GENBANK/L40397
  • GENBANK/L40398
  • GENBANK/L40399
  • GENBANK/L40400
  • GENBANK/L40401
  • GENBANK/L40402
  • GENBANK/L40403
  • GENBANK/L42110
  • GENBANK/L42177
  • GENBANK/L76517
  • GENBANK/L76518
  • GENBANK/L76519
  • GENBANK/L76520
  • GENBANK/L76521
  • GENBANK/L76522
  • GENBANK/L76523
  • GENBANK/L76524
  • GENBANK/L76525
  • GENBANK/L76526
  • GENBANK/L76527
  • GENBANK/L76528