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.
Bibliographical noteFunding Information:
Supported by NIA Grants AG05136 (Alzheimer's DiseaseR esearchC enterat the Universityo f Washington) and AG00029 (D. Pattersona nd K.P. Clancey),a nd NIMH Grant R01MH 43240 (H.T. Orr, J.A. White and L.L. Heston). Also supportedb y GM 15253 Veterans AdministratioRne searchF unds(T.D. Bird), the American Health AssistanceF oundation(T .D. Bird, G.D. Sch-ellenbergJ,R K and SMP) and the Alzheimer'sA ssocia-tion (D. Patterson)W. e thank S. O'dahl, L. AndersonE, . Loomis and S. Ito for technicalh elp, and A.D. Roses and the KatheleenB ryantA lzheimer'Ds iseaseR esearch Center provided some of the cell lines for family LH (603). Informedc onsentw as obtainedfr om each subject or next-of-kinw ith approvalo f the Universityo f Washington Human SubjectsR eviewCommittee.
Copyright 2014 Elsevier B.V., All rights reserved.
- Chromosome 14
- Familial Alzheimer's disease
- Linkage analysis
- Sequence analysis
- c-fos Gene