Comparative Genomics Identifies a Flagellar and Basal Body Proteome that Includes the BBS5 Human Disease Gene
نویسندگان
چکیده
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.
منابع مشابه
Comparative Genomics: Prediction of the Ciliary and Basal Body Proteome
Defects in mammalian cilia lead to a range of diseases, but our understanding of the composition of these organelles and of the basal bodies from which they arise is limited. Two recent studies used comparative genomics to predict the ciliary and basal body proteomes, providing datasets that are rich sources of human disease gene candidates.
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ورودعنوان ژورنال:
- Cell
دوره 117 شماره
صفحات -
تاریخ انتشار 2004