title: Identification and expression analysis of a potential familial Alzheimer disease gene on chromosome 1 related to AD3.
abstract: The inheritance of much early-onset Alzheimer disease (AD) has been linked to a dominant-acting locus on chromosome 14. Recently, the gene likely responsible for this genetic linkage has been identified and termed AD3. Five mutations have been found in AD3 that segregate with the disease phenotype in seven AD families and are not present in unaffected individuals. Here we report the existence of a gene encoding a seven transmembrane domain protein very similar to that encoded by AD3 in structure and sequence. This gene is located on chromosome 1, is expressed in a variety of tissues, including brain, and is predicted to harbor mutations causing nonchromosome 14 familial AD. The presence of several S/TPXX DNA binding motifs in both the AD3 protein and the AD3-like protein /AD4 protein suggests a possible role in intracellular signaling and gene expression or in linking chromatin to the nuclear membrane. Ways in which mutations in either gene could lead to AD are discussed.
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.forename: H
authors.initials: H
authors.lastname: Potter
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D000595:Amino Acid Sequence; D001665:Binding Sites; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism*; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast; D002878:Chromosomes, Human, Pair 1; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D009928:Organ Specificity; D053764:Presenilin-1; D053766:Presenilin-2; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid
chemical_list: D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D012333:RNA, Messenger