The grant detail shows the name of the PI, active dates of the project, the funding institute and the abstract of the grant. This abstract is what is used to create the fingerprint of the grant. If any publications referencing this grant are found in the data, they will be listed here as well.
Identification and Characterization of Novel AD Genes
1 April 1999 - 30 April 2013
NATIONAL INSTITUTE OF MENTAL HEALTH
Total Funding: $ 6,038,073
Since 1989, we have led the ascertainment,evaluation, and genetic analysesof the NIMH GeneticsInitiative Alzheimer's disease (AD) sample. This set of AD families, which currently includes 457 families, is the argest uniformly ascertained and evaluated sample assembled for the study of AD genetics. Over the first ive years of this R37, we have continued to carry out genetic analysesand follow-up studies of our a high- resolution whole genome genetic linkage screen for novel AD candidate genes. We have focused on linkage peaks identified on chromosomes 9 and 10, and identified late-onsetAD candidate genes in both ofthese inkage peaks: insulin degrading enzyme (IDE;10q) and ubiquilin 1 (UBQLN1;9q). In addition tofunctionally characterizing these genes for potential pathogenic effects in AD, we have built a highly efficient gene discovery pipeline, customized for large-scale generation, confirmation, storage and analysis of SNP genotype information. Our NIMH family-based association database of positional candidate gene contains over 500,000 genotypes for more than 300 SNPs in over 150 genestested in the full NIMH sample. Furthermore, we have recently obtained nearly one billion genotypes for the NIMH sample from a high- density, whole genome association screen using the Affymetrix 500K SNPchip, currently under analysis. By early October, we will also have obtained the results of a screen of the Affymetrix20,000 coding region SNPs (cSNPs) for the entire NIMH AD family sample. This screen should identify SNPs with a higher probability of potentially pathologenic effects.These combined data sets now provide anunprecedented array of AD candidate genes collectively accounting for as much as 95% of the genetic van'ability of AD. In the second half of this R37, we will carry out confirmatory and follow-up studies of these AD candidate genes. First, SNPs exhibiting family-basedassociation with AD will be confirmed by manual genotyping. Second, they will be confirmed in additional AD family-based samples. Third, tagging SNPs for all inkage disequilibrium blocks in confirmed candidate genes will be tested in the NIMH and confirmatory samples. Fourth, bioinformatic analyses and resequencing will be performed to identify potentially pathogenic mutations and gene variants. The strongest candidate genes will then be validated in a wide array of functional analyses to assess the potential pathogenicity of AD-associatedgene variants.
34 Resulting Publications
Xu Wu; Yan Lu; Yuanlin Dong; Guohua Zhang; Yiying Zhang; Zhipeng Xu; Deborah J Culley; Gregory Crosby; Edward R Marcantonio; Rudolph E Tanzi; et al.Neurobiology of aging 2012;33(7):1364-78.
Sungho Won; Qing Lu; Lars Bertram; Rudolph E Tanzi; Christoph LangeHuman heredity 2012;73(1):35-46.
A Li; C Zhou; J Moore; P Zhang; T H Tsai; H C Lee; D M Romano; M L McKee; D A Schoenfeld; M J Serra; et al.Current Alzheimer research 2011;8(3):313-22.
Can Zhang; Andrew Browne; Daniel Child; Jason R Divito; Jesse A Stevenson; Rudolph E TanziThe Journal of biological chemistry 2010;285(12):8515-26.
Davide Gianni; Airong Li; Giuseppina Tesco; Kenneth M McKay; John Moore; Kunal Raygor; Marcello Rota; Judith K Gwathmey; G William Dec; Thomas Aretz; et al.Circulation 2010;121(10):1216-26.
Vilmantas Giedraitis; Anna Glaser; Timo Sarajärvi; RoseMarie Brundin; Malin Degerman Gunnarsson; Brit-Maren Schjeide; Rudolph E Tanzi; Seppo Helisalmi; Tuula Pirttilä; Lena Kilander; et al.Neuroscience letters 2010;469(2):265-7.
Lars Bertram; Rudolph E TanziNature reviews. Neurology 2010;6(1):11-3.
Can Zhang; Andrew Browne; Jason R Divito; Jesse A Stevenson; Donna Romano; Yuanlin Dong; Zhongcong Xie; Rudolph E TanziJournal of Alzheimer's disease : JAD 2010;22(2):683-984.
David W Fardo; K David Becker; Lars Bertram; Rudolph E Tanzi; Christoph LangeEuropean journal of human genetics : EJHG 2009;17(12):1676-82.
Minji Kim; Jaehong Suh; Donna Romano; Mimy H Truong; Kristina Mullin; Basavaraj Hooli; David Norton; Giuseppina Tesco; Kathy Elliott; Steven L Wagner; et al.Human molecular genetics 2009;18(20):3987-96.
Brit-Maren M Schjeide; Matthew B McQueen; Kristina Mullin; Jason DiVito; Meghan F Hogan; Michele Parkinson; Basavaraj Hooli; Christoph Lange; Deborah Blacker; Rudolph E Tanzi; et al.Neurogenetics 2009;10(1):19-25.
Brit-Maren M Schjeide; Basavaraj Hooli; Michele Parkinson; Meghan F Hogan; Jason DiVito; Kristina Mullin; Deborah Blacker; Rudolph E Tanzi; Lars BertramArchives of neurology 2009;66(2):250-4.
Lars Bertram; Brit-Maren M Schjeide; Basavaraj Hooli; Kristina Mullin; Mikko Hiltunen; Hilkka Soininen; Martin Ingelsson; Lars Lannfelt; Deborah Blacker; Rudolph E TanziCell 2008;135(6):993-4; author reply 994-6.
Zhongcong Xie; Deborah J Culley; Yuanlin Dong; Guohua Zhang; Bin Zhang; Robert D Moir; Matthew P Frosch; Gregory Crosby; Rudolph E TanziAnnals of neurology 2008;64(6):618-27.
Lars Bertram; Rudolph E TanziNature reviews. Neuroscience 2008;9(10):768-78.
In Ho Lee; Deborah J Culley; Mark G Baxter; Zhongcong Xie; Rudolph E Tanzi; Gregory CrosbyAnesthesia and analgesia 2008;107(4):1211-5.
Barbara A J Schaffer; Lars Bertram; Bruce L Miller; Kristina Mullin; Sandra Weintraub; Nancy Johnson; Eileen H Bigio; Marsel Mesulam; Martina Wiedau-Pazos; George R Jackson; et al.Archives of neurology 2008;65(10):1368-74.
Rudolph E TanziNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 2008;5(3):377-80.
Bin Zhang; Yuanlin Dong; Guohua Zhang; Robert D Moir; Weiming Xia; Yun Yue; Ming Tian; Deborah J Culley; Gregory Crosby; Rudolph E Tanzi; et al.The Journal of biological chemistry 2008;283(18):11866-75.
Guohua Zhang; Yuanlin Dong; Bin Zhang; Fumito Ichinose; Xu Wu; Deborah J Culley; Gregory Crosby; Rudolph E Tanzi; Zhongcong XieThe Journal of neuroscience : the official journal of the Society for Neuroscience 2008;28(17):4551-60.
Airong Li; Zhongcong Xie; Yuanlin Dong; Kenneth M McKay; Mary L McKee; Rudolph E TanziHuman molecular genetics 2007;16(21):2626-39.
Giuseppina Tesco; Young Ho Koh; Eugene L Kang; Andrew N Cameron; Shinjita Das; Miguel Sena-Esteves; Mikko Hiltunen; Shao-Hua Yang; Zhenyu Zhong; Yong Shen; et al.Neuron 2007;54(5):721-37.
Zhongcong Xie; Yuanlin Dong; Uta Maeda; Weiming Xia; Rudolph E TanziThe Journal of biological chemistry 2007;282(7):4318-25.
Zhongcong Xie; Yuanlin Dong; Uta Maeda; Robert D Moir; Weiming Xia; Deborah J Culley; Gregory Crosby; Rudolph E TanziThe Journal of neuroscience : the official journal of the Society for Neuroscience 2007;27(6):1247-54.
Zhongcong Xie; Yuanlin Dong; Uta Maeda; Robert Moir; Sharon K Inouye; Deborah J Culley; Gregory Crosby; Rudolph E TanziThe journals of gerontology. Series A, Biological sciences and medical sciences 2006;61(12):1300-6.
Deborah J Culley; Rustam Y Yukhananov; Zhongcong Xie; Reddy R Gali; Rudolph E Tanzi; Gregory CrosbyEuropean journal of pharmacology 2006;549(1-3):71-8.
Deborah Blacker; Simon LovestoneJournal of geriatric psychiatry and neurology 2006;19(3):186-91.
Donna M Romano; Yuanlin Dong; Mikko Hiltunen; Rudolph E Tanzi; Zhongcong XieAmyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis 2006;13(2):86-92.
Zhongcong Xie; Yuanlin Dong; Uta Maeda; Paul Alfille; Deborah J Culley; Gregory Crosby; Rudolph E TanziAnesthesiology 2006;104(5):988-94.
Zhongcong Xie; Rudolph E TanziExperimental gerontology 2006;41(4):346-59.
Zhongcong Xie; Donna M Romano; Rudolph E TanziThe Journal of biological chemistry 2005;280(15):15413-21.
Zhongcong Xie; Donna M Romano; Rudolph E TanziJournal of molecular neuroscience : MN 2005;25(1):67-77.
Zhongcong Xie; Donna M Romano; Dora M Kovacs; Rudolph E TanziThe Journal of biological chemistry 2004;279(33):34130-7.
J D Buxbaum; C Lilliehook; J Y Chan; R C Go; S S Bassett; R E Tanzi; W Wasco; D BlackerNeuroscience letters 2000;294(3):135-8.
This section shows information that has been computed by using the fingerprint of the grant, including related publications, related experts and related grants - all with fingerprints representing significant amounts of overlap between their fingerprint and this grant. The red dots indicate whether those experts or terms actually appear within this grant, showing potential and actual connections.
Appears in this Publication
Author of this Publication