title: Genomic structure and expression of STM2, the chromosome 1 familial Alzheimer disease gene.
abstract: Mutations in the gene STM2 result in autosomal dominant familial Alzheimer disease. To screen for mutations and to identify regulatory elements for this gene, the genomic DNA sequence and intron-exon structure were determined. Twelve exons including 10 coding exons were identified in a genomic region spanning 23,737 bp. The first 2 exons encode the 5'-untranslated region. Expression analysis of STM2 indicates that two transcripts of 2.4 and 2.8 kb are found in skeletal muscle, pancreas, and heart. In addition, a splice variant of the 2.4-kb transcript was identified that is the result of the use of an alternative splice acceptor site located in exon 10. The use of this site results in a transcript lacking a single glutamate. The promotor for this gene and the alternatively spliced exons leading to the 2.8-kb form of the gene remain to be identified. Expression of STM2 was high in skeletal muscle and pancreas, with comparatively low levels observed in brain. This expression pattern is intriguing since in Alzheimer disease, pathology and degeneration are observed only in the central nervous system.
authors.affiliation: Division of Medical Genetics, University of Washington, Seattle, Washington, 98195, USA.
authors.forename: E
authors.initials: E
authors.lastname: Levy-Lahad
authors.forename: P
authors.initials: P
authors.lastname: Poorkaj
authors.forename: K
authors.initials: K
authors.lastname: Wang
authors.forename: Y H
authors.initials: YH
authors.lastname: Fu
authors.forename: J
authors.initials: J
authors.lastname: Oshima
authors.forename: J
authors.initials: J
authors.lastname: Mulligan
authors.forename: G D
authors.initials: GD
authors.lastname: Schellenberg
mesh_terms: D017398:Alternative Splicing; D000544:Alzheimer Disease / Q000235:genetics*; D000595:Amino Acid Sequence; D017209:Apoptosis; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D003001:Cloning, Molecular; D017931:DNA Primers; D006801:Humans; D007438:Introns; D008565:Membrane Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009928:Organ Specificity; D010179:Pancreas / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D053766:Presenilin-2; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D012045:Regulatory Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D008565:Membrane Proteins; C508861:PSEN2 protein, human; D053766:Presenilin-2; C095101:Psen2 protein, mouse; D011994:Recombinant Proteins