Elsevier

Neuroscience Letters

Volume 174, Issue 1, 6 June 1994, Pages 97-100
Neuroscience Letters

Genetic analysis of the cellular oncogene fos in patients with chromosome 14 encoded Alzheimer's disease

https://doi.org/10.1016/0304-3940(94)90128-7Get rights and content

Abstract

A major gene for familial early-ons et Alzheimer's disease (AD) has been localised to chromosome 14q24.3. The c-fos gene (FOS), localised to 14q24.3-q31, is a candidate for the AD gene since it may be involved in the transcription regulation of the amyloid precursor protein gene (APP). Part of APP codes for the βA4 amyloid present in AD brain lesions. We analyzed linkage of AD in the 2 early-onset AD families, AD/A and AD/B, using a polymerase chain reaction (PCR) based assay for a restriction fragment length polymorphism (RFLP). The RFLP is detected in BstNI digested DNA and is located near the 3′ end of FOS. No obligate recombinants were detected. The 4 exons of FOS were sequenced in one pathologically confirmed AD patient in each family. No exonic mutations were found. Two intronic sequence variations were observed, one in intron 2 and one in intron 3. The intron 2 variation did not segregate with AD. The intron 3 variation which is a single G insertion was used in linkage studies in families AD/A and AD/B and showed conclusive linkage in both families in the absence of recombinants. Therefore, FOS cannot yet be excluded as a candidate gene for AD in these families since mutations may be present in regulatory sequences.

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