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Citation
Shulman, J.M., Chipendo, P., Chibnik, L.B., Aubin, C., Tran, D., Keenan, B.T., Kramer, P.L., Schneider, J.A., Bennett, D.A., Feany, M.B., De Jager, P.L. (2011). Functional Screening of Alzheimer Pathology Genome-wide Association Signals in Drosophila.  Am. J. Hum. Genet. 88(2): 232--238.
FlyBase ID
FBrf0212981
Publication Type
Research paper
Abstract
We have leveraged a Drosophila model relevant to Alzheimer disease (AD) for functional screening of findings from a genome-wide scan for loci associated with a quantitative measure of AD pathology in humans. In six of the 15 genomic regions evaluated, we successfully identified a causal gene for the association, on the basis of in vivo interactions with the neurotoxicity of Tau, which forms neurofibrillary tangles in AD. Among the top results, rs10845990 within SLC2A14, encoding a glucose transporter, showed evidence of replication for association with AD pathology, and gain and loss of function in glut1, the Drosophila ortholog, was associated with suppression and enhancement of Tau toxicity, respectively. Our strategy of coupling genome-wide association in humans with functional screening in a model organism is likely to be a powerful approach for gene discovery in AD and other complex genetic disorders.
PubMed ID
PubMed Central ID
PMC3035702 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Am. J. Hum. Genet.
    Title
    American Journal of Human Genetics
    Publication Year
    1949-
    ISBN/ISSN
    0002-9297
    Data From Reference