Analysis of the 5' sequence, genomic structure, and alternative splicing of the presenilin-1 gene (PSEN1) associated with early onset Alzheimer disease.

摘要: Mutations in the human presenilin genes (PSEN1 and PSEN2) are associated with early onset familial Alzheimer disease. The encode integral membrane proteins similar structures, which suggests that they may have closely related, but as yet unknown functions. Analysis of 5' upstream sequence structure PSEN1 gene reveals contains multiple putative transcription regulatory elements including clusters STAT involved transcriptional activation response to signal transduction. first four exons contain untranslated sequences, Exons 1 2 representing alternate initial sites. function these is unclear. Exon 4 bears ATG sequence. last 12 bp used an alternative splice donor site. 9 alternately spliced leukocytes, not most other tissues. Splicing predicted cause significant structural changes protein. majority transcripts expressed tissues polyadenylated 1127 from TAG stop codon 13. A small proportion same 5'UTR ORF 4435 codon. longer three additional palindromes at least one stem-loop stabilities greater than -16 kcal/mol.