title: Comparative genomics identifies a flagellar and basal body proteome that includes the BBS5 human disease gene.
abstract: Cilia and flagella are microtubule-based structures nucleated by modified centrioles termed basal bodies. These biochemically complex organelles have more than 250 and 150 polypeptides, respectively. To identify the proteins involved in ciliary and basal body biogenesis and function, we undertook a comparative genomics approach that subtracted the nonflagellated proteome of Arabidopsis from the shared proteome of the ciliated/flagellated organisms Chlamydomonas and human. We identified 688 genes that are present exclusively in organisms with flagella and basal bodies and validated these data through a series of in silico, in vitro, and in vivo studies. We then applied this resource to the study of human ciliation disorders and have identified BBS5, a novel gene for Bardet-Biedl syndrome. We show that this novel protein localizes to basal bodies in mouse and C. elegans, is under the regulatory control of daf-19, and is necessary for the generation of both cilia and flagella.
authors.affiliation: Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Jin Billy
authors.initials: JB
authors.lastname: Li
authors.forename: Jantje M
authors.initials: JM
authors.lastname: Gerdes
authors.forename: Courtney J
authors.initials: CJ
authors.lastname: Haycraft
authors.forename: Yanli
authors.initials: Y
authors.lastname: Fan
authors.forename: Tanya M
authors.initials: TM
authors.lastname: Teslovich
authors.forename: Helen
authors.initials: H
authors.lastname: May-Simera
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.forename: Oliver E
authors.initials: OE
authors.lastname: Blacque
authors.forename: Linya
authors.initials: L
authors.lastname: Li
authors.forename: Carmen C
authors.initials: CC
authors.lastname: Leitch
authors.forename: Richard Allan
authors.initials: RA
authors.lastname: Lewis
authors.forename: Jane S
authors.initials: JS
authors.lastname: Green
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Parfrey
authors.forename: Michel R
authors.initials: MR
authors.lastname: Leroux
authors.forename: William S
authors.initials: WS
authors.lastname: Davidson
authors.forename: Philip L
authors.initials: PL
authors.lastname: Beales
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Guay-Woodford
authors.forename: Bradley K
authors.initials: BK
authors.lastname: Yoder
authors.forename: Gary D
authors.initials: GD
authors.lastname: Stormo
authors.forename: Nicholas
authors.initials: N
authors.lastname: Katsanis
authors.forename: Susan K
authors.initials: SK
authors.lastname: Dutcher
mesh_terms: D000818:Animals; D017360:Arabidopsis; D020788:Bardet-Biedl Syndrome / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D002696:Chlamydomonas; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002923:Cilia / Q000235:genetics* / Q000378:metabolism; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D005260:Female; D005407:Flagella / Q000235:genetics* / Q000378:metabolism; D015698:Genomic Library; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D028044:Phosphate-Binding Proteins; D011506:Proteins / Q000235:genetics* / Q000302:isolation & purification; D020543:Proteome / Q000235:genetics*; D034622:RNA Interference; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics
chemical_list: C487434:BBS5 protein, human; D029742:Caenorhabditis elegans Proteins; D003598:Cytoskeletal Proteins; C410596:DAF-19 protein, C elegans; D018076:DNA, Complementary; D028044:Phosphate-Binding Proteins; D011506:Proteins; D020543:Proteome; D014157:Transcription Factors