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Molecular Analysis of the Presenilin 1 (S182) Gene in “Sporadic” Cases of Alzheimer's Disease: Identification and Characterisation of Unusual Splice Variants
Author(s) -
Anwar Rashida,
Moynihan Terry P.,
Ardley Helen,
Brindle Nicholas,
Coletta P. Louise,
Cairns Nigel,
Markham Alexander F.,
Robinson Philip A.
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.66041774.x
Subject(s) - presenilin , identification (biology) , splice , disease , gene , genetics , biology , alzheimer's disease , computational biology , medicine , pathology , botany
Mutations of the presenilin 1 (PS‐1) gene at the Alzheimer's disease (AD) FAD3 locus on chromosome 14q24.3 are responsible for the majority of familial early‐onset AD. As genes responsible for familial forms of AD are obvious candidates for further investigation in “sporadic” disease, we performed a molecular analysis of PS‐1 transcripts extracted from brain tissues of a series of histologically confirmed cases of “sporadic” AD (n = 10) and also from histologically “normal” (non‐Alzheimer) age‐matched brain controls (n = 5). No sequence changes in the PS‐1 coding sequence were detected after analysis by reverse transcription‐PCR. This suggests that the frequency of mutations in the PS‐1 (S182) coding region in “sporadic” Alzheimer's disease is very low. However, we demonstrated that the PS‐1 gene is highly variably spliced. One splice variant involves the 5′ untranslated region of the PS‐1 gene only and hence encodes for normal PS‐1. Six further splice variants involve coding regions of the PS‐1 gene and result in truncated proteins lacking specific transmembrane domains. Most of these variants do not coincide with recognized sites of introns in the PS‐1 gene. One of these variants, resulting in the loss of transmembrane domain TM‐VII, was found only in an AD patient.