Identification and Confirmation of an Exonic Splicing Enhancer Variation in Exon 5 of the Alzheimer Disease Associated PICALM Gene

被引:16
作者
Schnetz-Boutaud, Nathalie C. [1 ,2 ]
Hoffman, Joshua [1 ,2 ]
Coe, Jared E. [1 ,2 ]
Murdock, Deborah G. [1 ,2 ]
Pericak-Vance, Margaret A. [3 ]
Haines, Jonathan L. [1 ,2 ]
机构
[1] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Med Ctr, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA
[3] Univ Miami, Miller Sch Med, Hussman Inst Human Genom, Miami, FL 33136 USA
关键词
Alzheimer; neurodegenerative disease; PICALM; sequencing; exonic splicing; GENOME-WIDE ASSOCIATION; COMMON VARIANTS; CR-1; CLU; PROTEIN; ALLELE; CD2AP; EPHA1; CALM; RISK;
D O I
10.1111/j.1469-1809.2012.00727.x
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页码:448 / 453
页数:6
相关论文
共 26 条
[1]   Distribution and Expression of Picalm in Alzheimer Disease [J].
Baig, Shabnam ;
Joseph, Sally A. ;
Tayler, Hannah ;
Abraham, Richard ;
Owen, Michael J. ;
Williams, Julie ;
Kehoe, Patrick G. ;
Love, Seth .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2010, 69 (10) :1071-1077
[2]   Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database [J].
Bertram, Lars ;
McQueen, Matthew B. ;
Mullin, Kristina ;
Blacker, Deborah ;
Tanzi, Rudolph E. .
NATURE GENETICS, 2007, 39 (01) :17-23
[3]   Molecular genetics of Alzheimer's disease: An update [J].
Brouwers, Nathalie ;
Sleegers, Kristel ;
Van Broeckhoven, Christine .
ANNALS OF MEDICINE, 2008, 40 (08) :562-583
[4]   Replication of CLU, CR1, and PICALM Associations With Alzheimer Disease [J].
Carrasquillo, Minerva M. ;
Belbin, Olivia ;
Hunter, Talisha A. ;
Ma, Li ;
Bisceglio, Gina D. ;
Zou, Fanggeng ;
Crook, Julia E. ;
Pankratz, V. Shane ;
Dickson, Dennis W. ;
Graff-Radford, Neill R. ;
Petersen, Ronald C. ;
Morgan, Kevin ;
Younkin, Steven G. .
ARCHIVES OF NEUROLOGY, 2010, 67 (08) :961-964
[5]   Listening to silence and understanding nonsense: Exonic mutations that affect splicing [J].
Cartegni, L ;
Chew, SL ;
Krainer, AR .
NATURE REVIEWS GENETICS, 2002, 3 (04) :285-298
[6]   ESEfinder: a web resource to identify exonic splicing enhancers [J].
Cartegni, L ;
Wang, JH ;
Zhu, ZW ;
Zhang, MQ ;
Krainer, AR .
NUCLEIC ACIDS RESEARCH, 2003, 31 (13) :3568-3571
[7]   CR1 Is Associated with Amyloid Plaque Burden and Age-Related Cognitive Decline [J].
Chibnik, Lori B. ;
Shulman, Joshua M. ;
Leurgans, Sue E. ;
Schneider, Julie A. ;
Wilson, Robert S. ;
Tran, Dong ;
Aubin, Cristin ;
Buchman, Aron S. ;
Heward, Christopher B. ;
Myers, Amanda J. ;
Hardy, John A. ;
Huentelman, Matthew J. ;
Corneveaux, Jason J. ;
Reiman, Eric M. ;
Evans, Denis A. ;
Bennett, David A. ;
De Jager, Philip L. .
ANNALS OF NEUROLOGY, 2011, 69 (03) :560-569
[8]   PROTECTIVE EFFECT OF APOLIPOPROTEIN-E TYPE-2 ALLELE FOR LATE-ONSET ALZHEIMER-DISEASE [J].
CORDER, EH ;
SAUNDERS, AM ;
RISCH, NJ ;
STRITTMATTER, WJ ;
SCHMECHEL, DE ;
GASKELL, PC ;
RIMMLER, JB ;
LOCKE, PA ;
CONNEALLY, PM ;
SCHMADER, KE ;
SMALL, GW ;
ROSES, AD ;
HAINES, JL ;
PERICAKVANCE, MA .
NATURE GENETICS, 1994, 7 (02) :180-184
[9]   GENE DOSE OF APOLIPOPROTEIN-E TYPE-4 ALLELE AND THE RISK OF ALZHEIMERS-DISEASE IN LATE-ONSET FAMILIES [J].
CORDER, EH ;
SAUNDERS, AM ;
STRITTMATTER, WJ ;
SCHMECHEL, DE ;
GASKELL, PC ;
SMALL, GW ;
ROSES, AD ;
HAINES, JL ;
PERICAKVANCE, MA .
SCIENCE, 1993, 261 (5123) :921-923
[10]   Association of CR1, CLU and PICALM with Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals [J].
Corneveaux, Jason J. ;
Myers, Amanda J. ;
Allen, April N. ;
Pruzin, Jeremy J. ;
Ramirez, Manuel ;
Engel, Anzhelika ;
Nalls, Michael A. ;
Chen, Kewei ;
Lee, Wendy ;
Chewning, Kendria ;
Villa, Stephen E. ;
Meechoovet, Hunsar B. ;
Gerber, Jill D. ;
Frost, Danielle ;
Benson, Hollie L. ;
O'Reilly, Sean ;
Chibnik, Lori B. ;
Shulman, Joshua M. ;
Singleton, Andrew B. ;
Craig, David W. ;
Van Keuren-Jensen, Kendall R. ;
Dunckley, Travis ;
Bennett, David A. ;
De Jager, Philip L. ;
Heward, Christopher ;
Hardy, John ;
Reiman, Eric M. ;
Huentelman, Matthew J. .
HUMAN MOLECULAR GENETICS, 2010, 19 (16) :3295-3301