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Joubert syndrome and related disorders (JSRD) are primarily autosomal-recessive conditions characterized by hypotonia, ataxia, abnormal eye movements, and intellectual disability with a distinctive mid-hindbrain malformation. Variable features include retinal dystrophy, cystic kidney disease, and liver fibrosis. JSRD are included in the rapidly expanding group of disorders called ciliopathies, because all six gene products implicated in JSRD (NPHP1, AHI1, CEP290, RPGRIP1L, TMEM67, and ARL13B) function in the primary cilium/basal body organelle. By using homozygosity mapping in consanguineous families, we identify loss-of-function mutations in CC2D2A in JSRD patients with and without retinal, kidney, and liver disease. CC2D2A is expressed in all fetal and adult tissues tested. In ciliated cells, we observe localization of recombinant CC2D2A at the basal body and colocalization with CEP290, whose cognate gene is mutated in multiple hereditary ciliopathies. In addition, the proteins can physically interact in vitro, as shown by yeast two-hybrid and GST pull-down experiments. A nonsense mutation in the zebrafish CC2D2A ortholog (sentinel) results in pronephric cysts, a hallmark of ciliary dysfunction analogous to human cystic kidney disease. Knockdown of cep290 function in sentinel fish results in a synergistic pronephric cyst phenotype, revealing a genetic interaction between CC2D2A and CEP290 and implicating CC2D2A in cilium/basal body function. These observations extend the genetic spectrum of JSRD and provide a model system for studying extragenic modifiers in JSRD and other ciliopathies.
Pubmed ID: 18950740 RIS Download
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Web-service providing access to database that brings together information from broad range of resources. Web application for functional annotation and statistical hypothesis testing. Provides tools for analysis of genomic and microarray data. Collection of tools include Bibliographic Information,Databases,Gene Annotation,Gene Regulation, Microarray,Proteins,Sequence Manipulation - Nucleic Acids,Sequence Manipulation - Protein, Systems Biology.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on February 28,2023. This server takes a multiple-alignment file in either GCG''s MSF-format or Clustals ALN-format. Sponsors: This resource was supported by the Swiss EMBnet Node Server. Keywords: Server, Multiple-alignment,
View all literature mentionsA database of phylogenetic trees of animal genes. It aims at developing a curated resource that gives reliable information about ortholog and paralog assignments, and evolutionary history of various gene families. TreeFam defines a gene family as a group of genes that evolved after the speciation of single-metazoan animals. It also tries to include outgroup genes like yeast (S. cerevisiae and S. pombe) and plant (A. thaliana) to reveal these distant members.TreeFam is also an ortholog database. Unlike other pairwise alignment based ones, TreeFam infers orthologs by means of gene trees. It fits a gene tree into the universal species tree and finds historical duplications, speciations and losses events. TreeFam uses this information to evaluate tree building, guide manual curation, and infer complex ortholog and paralog relations.The basic elements of TreeFam are gene families that can be divided into two parts: TreeFam-A and TreeFam-B families. TreeFam-B families are automatically created. They might contain errors given complex phylogenies. TreeFam-A families are manually curated from TreeFam-B ones. Family names and node names are assigned at the same time. The ultimate goal of TreeFam is to present a curated resource for all the families. phylogenetic tree, animal, vertebrate, invertebrate, gene, ortholog, paralog, evolutionary history, gene families, single-metazoan animals, outgroup genes like yeast (S. cerevisiae and S. pombe), plant (A. thaliana), historical duplications, speciations, losses, Human, Genome, comparative genomics
View all literature mentionsSoftware application with data analysis tools and spreadsheet templates to track and visualize data. It is used to manage and process data.
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
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