title: Identification and confirmation of an exonic splicing enhancer variation in exon 5 of the Alzheimer disease associated PICALM gene.
abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory and cognitive impairment and is the leading cause of dementia in the elderly. A number of genome wide association studies and subsequent replication studies have been published recently on late onset AD (LOAD). These studies identified several new susceptibility genes including phosphatidylinositol-binding clathrin assembly protein (PICALM) on chromosome 11. The aim of our study was to examine the entire coding sequence of PICALM to determine if the association could be explained by any previously undetected sequence variation. Therefore, we sequenced 48 cases and 48 controls homozygous for the risk allele in the signal SNP rs3851179. We did not find any new variants; however, rs592297, a known coding synonymous SNP that is part of an exonic splice enhancer region in exon 5, is in strong linkage disequilibrium with rs3851179 and should be examined for functional significance in Alzheimer pathophysiology.
authors.affiliation: Center for Human Genetics Research and Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Nathalie C
authors.initials: NC
authors.lastname: Schnetz-Boutaud
authors.forename: Joshua
authors.initials: J
authors.lastname: Hoffman
authors.forename: Jared E
authors.initials: JE
authors.lastname: Coe
authors.forename: Deborah G
authors.initials: DG
authors.lastname: Murdock
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D001483:Base Sequence; D019295:Computational Biology / Q000379:methods; D005091:Exons; D023061:Gene Order; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D008969:Molecular Sequence Data; D034041:Monomeric Clathrin Assembly Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012326:RNA Splicing; D038621:Regulatory Sequences, Ribonucleic Acid
chemical_list: D034041:Monomeric Clathrin Assembly Proteins; C439003:PICALM protein, human; D038621:Regulatory Sequences, Ribonucleic Acid