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General Information
Name
Alzheimer disease, susceptibility to (postulated), CELF1-related
FlyBase ID
FBhh0000262
Disease Ontology Term
Parent Disease
OMIM
Overview

Initially identified in an analysis of two genome-wide association studies (FBrf0223922), the human gene CELF1 is proposed as a candidate susceptibility locus for Alzheimer disease. CELF1 encodes an RNA-binding protein implicated in the regulation of several post-transcriptional events. There is a single fly ortholog, bru1, for which classical amorphic and hypomorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\bru1 is orthologous to one additional human gene, CELF2.

The CELF1 gene has not been introduced into flies.

The fly ortholog bru1 was tested for genetic interaction with a transgenically introduced mutational variant of the human tau gene (Hsap\MAPT): RNAi-mediated reduction in the expression of bru1 was observed to enhance the phenotype associated with tau toxicity; overexpression in the eye reduces the tau toxicity phenotype. Loss-of-function alleles of Dmel\bru1 are typically female sterile and exhibit defects in indirect flight muscles. Physical and genetic interactions of Dmel\bru1 have been characterized; see below and in the gene report for bru1.

[updated June 2016 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: Alzheimer disease
Symptoms and phenotype
Alzheimer disease (AD) is the most common form of progressive dementia in the elderly. [from OMIM:104300; 2016.01.08]
Memory loss is the most common sign of Alzheimer disease. As the disorder progresses, some people with AD experience personality and behavioral changes; other common symptoms include agitation, restlessness, withdrawal, and loss of language skills. Total care is usually required during the advanced stages of the disease. Affected individuals usually survive 8 to 10 years after the appearance of symptoms, but the course of the disease can range from 1 to 25 years. Death usually results from pneumonia, malnutrition, or general body wasting. [from Genetics Home Reference, Alzheimer disease; 2016.01.08]
Alzheimer disease can be classified as early-onset or late-onset. The signs and symptoms of the early-onset form appear before age 65, while the late-onset form appears after age 65. The early-onset form is much less common than the late-onset form, accounting for less than 5 percent of all cases of Alzheimer disease. [from Genetics Home Reference, Alzheimer disease; 2016.01.08]
Specific Disease Summary: Alzheimer disease, susceptibility to (postulated), CELF1-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Locus identified as showing significant association with susceptibility to Alzheimer disease in an analysis of two genome-wide association studies (GWAS).
CELF1 is associated with late-onset Alzheimer disease in a GWAS study (see GWAS Catalog, below in 'External links').
Cellular phenotype and pathology
Molecular information
CELF1 encodes an RNA-binding protein implicated in the regulation of several post-transcriptional events, including pre-mRNA alternative splicing, mRNA translation and stability. [from Gene Cards, CELF1; 2016.06.02]
External links
Disease synonyms
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)
    Many to many: 2 human to 2 Drosophila; additional high-scoring human ortholog is CELF2.
    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Gene Snapshot
      bruno 1 (bru1) encodes an RNA binding protein acting in multiple forms of post-transcriptional gene regulation including repression and activation of translation and alternative splicing of pre-mRNAs. The product of bru1 is required for gametogenesis, developmental patterning, and muscle organization. [Date last reviewed: 2018-09-06]
      Gene Groups / Pathways
        Comments on ortholog(s)
        Higher-scoring Drosophila ortholog of human genes CELF1 and CELF2 (2 Drosophila to 2 human). Dmel\bru1 shares 46-49% identity and 57-62% similarity with the human genes.
        Orthologs and Alignments from DRSC
        DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
        Synthetic Gene(s) Used (0)
        Summary of Physical Interactions (17 groups)
        RNA-protein
        Interacting group
        Assay
        References
        iclip, partial RNA sequence identification
        systematic evolution of ligands by exponential enrichment, full identification by DNA sequencing, electrophoretic mobility shift assay, autoradiography
        pull down, autoradiography
        anti bait coimmunoprecipitation, nucleic acid uv cross-linking assay, autoradiography
        electrophoretic mobility shift assay, autoradiography, nucleic acid uv cross-linking assay, western blot, pull down, anti tag western blot, anti bait coimmunoprecipitation, quantitative reverse transcription pcr
        electrophoretic mobility shift assay, autoradiography, anti bait coimmunoprecipitation, quantitative reverse transcription pcr
        anti bait coimmunoprecipitation, quantitative reverse transcription pcr
        electrophoretic mobility shift assay, autoradiography
        protein-protein
        Interacting group
        Assay
        References
        pull down, anti tag western blot
        anti bait coimmunoprecipitation, western blot
        anti bait coimmunoprecipitation, western blot, pull down, anti tag western blot, two hybrid
        anti bait coimmunoprecipitation, western blot
        anti bait coimmunoprecipitation, western blot
        anti bait coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation, western blot
        pull down, autoradiography, anti bait coimmunoprecipitation, western blot
        pull down, western blot
        Alleles Reported to Model Human Disease (Disease Ontology) (0 alleles)
        Genetic Tools, Stocks and Reagents
        Sources of Stocks
        Contact lab of origin for a reagent not available from a public stock center.
        Bloomington Stock Center Disease Page
        Selected mammalian transgenes
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila transgenes
        Allele
        Transgene
        Publicly Available Stocks
        RNAi constructs available
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila classical alleles
        Allele
        Allele class
        Mutagen
        Publicly Available Stocks
        loss of function allele
        ethyl methanesulfonate
        loss of function allele
        ethyl methanesulfonate
        References (6)