THE C-FOS GENE AND EARLY-ONSET FAMILIAL ALZHEIMERS-DISEASE

A gene for early-onset familial Alzheimer's disease (FAD) is located o n 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 ob served for linkage of this marker to FAD. DNA sequence analysis was us ed to examine FOS in two affected subjects from an FAD family in which the chromosome 14 FAD locus is clearly responsible for the disease. T he 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 althoug h we cannot exclude the possibility that a mutation in an as yet unkno wn regulatory region is responsible for the disease. A new polymorphis m was detected in the third intron of the gene.