The c-fos gene and early-onset familial Alzheimer's disease

Lori L.C. Bonnycastle, Chang En Yu, Ellen M. Wijsman, Harry T. Orr, David Patterson, Kevin P. Clancy, Katrina A.B. Goddard, M. Elisa Alonso, Ellen Nemens, June A. White, Leonard L. Heston, George M. Martin, Thomas D. Bird, Gerard D. Schellenberg

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

A gene for early-onset familial Alzheimer's disease (FAD) is located on chromosome 14q24.3. The c-fos gene (FOS) is also located in the same band of this chromosome and is thus a candidate for the FAD locus. A yeast artificial chromosome (YAC) clone was identified which contains FOS. This YAC also contains the short-tandem repeat polymorphic (STRP) locus D14S76, placing FOS in the FAD region between D14S53 and D14S43. No recombinants were observed between D14S76 and FAD, and a maximum positive LOD score of 7.20 at a recombination fraction of 0.001 was observed for linkage of this marker to FAD. DNA sequence analysis was used to examine FOS in two affected subjects from an FAD family in which the chromosome 14 FAD locus is clearly responsible for the disease. The coding regions and parts of the 5′ and 3′ untranslated sequences of FOS were sequenced; no FAD-related mutations were observed. This work suggests that the FOS gene is not the chromosome 14 FAD locus although we cannot exclude the possibility that a mutation in an as yet unknown regulatory region is responsible for the disease. A new polymorphism was detected in the third intron of the gene.

Original languageEnglish (US)
Pages (from-to)33-36
Number of pages4
JournalNeuroscience Letters
Volume160
Issue number1
DOIs
StatePublished - Sep 17 1993

Keywords

  • Chromosome 14
  • FOS
  • Familial Alzheimer's disease
  • Linkage analysis
  • Sequence analysis
  • c-fos Gene

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