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Neural tube defects (NTDs) are severe malformations of the central nervous system, affecting 1 of 1,000 live births. Mouse models were instrumental in defining the signaling pathways defective in NTDs, including the planar cell polarity (PCP), also called noncanonical Frizzled/Disheveled pathway. Based on the highly penetrant occurrence of NTDs in double Fzd3/Fzd6(-/-) mutant mice, we investigated the role of the human orthologues, FZD3 and FZD6, by resequencing a cohort of 473 NTDs patients and 639 ethnically matched controls. While we could not demonstrate a significant contribution of FZD3 gene, we identified five rare FZD6 variants that were absent in all controls and predicted to have a functional effect by computational analysis: one de novo frameshift mutation (c.1843_1844insA), three missense changes (p.Arg405Gln, p.Arg511Cys p.Arg511His), and one substitution (c.*20C>T) affecting the 3'-untranslated region (UTR) of the gene. The overall rate of predicted deleterious variants of FZD6 was 5.1-fold higher in cases compared to controls, resulting in a significantly increased NTDs mutation burden. This study demonstrates that rare nonsynonymous variants in FZD6 may contribute to NTDs in humans and enlarges the spectrum of mutations that link PCP pathway to NTDs.
Pubmed ID: 22045688
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Collection of data of protein sequence and functional information. Resource for protein sequence and annotation data. Consortium for preservation of the UniProt databases: UniProt Knowledgebase (UniProtKB), UniProt Reference Clusters (UniRef), and UniProt Archive (UniParc), UniProt Proteomes. Collaboration between European Bioinformatics Institute (EMBL-EBI), SIB Swiss Institute of Bioinformatics and Protein Information Resource. Swiss-Prot is a curated subset of UniProtKB.
View all literature mentionsSystem that classifies genes by their functions, using published scientific experimental evidence and evolutionary relationships to predict function even in absence of direct experimental evidence. Orthologs view is curated orthology relationships between genes for human, mouse, rat, fish, worm, and fly.
View all literature mentionsDatabase of Locus Specific Mutation Databases. Fields include HGNC Gene symbol / OMIM No., Database name / Internet address, and Curators. If you wish to add an LSDB please go to the LSDB Submission Page.
View all literature mentionsDatabase of microRNA target predictions and expression profiles. Target predictions are based on a development of the miRanda algorithm which incorporates current biological knowledge on target rules and on the use of an up-to-date compendium of mammalian microRNAs. MicroRNA expression profiles are derived from a comprehensive sequencing project of a large set of mammalian tissues and cell lines of normal and disease origin. This website enables users to explore: * The set of genes that are potentially regulated by a particular microRNA. * The implied cooperativity of multiple microRNAs on a particular mRNA. * MicroRNA expression profiles in various mammalian tissues. The web resource provides users with functional information about the growing number of microRNAs and their interaction with target genes in many species and facilitates novel discoveries in microRNA gene regulation. The microRNA Target Detection Software, miRanda, is an algorithm for finding genomic targets for microRNAs. This algorithm has been written in C and is available as an open-source method under the GPL.
View all literature mentionsGroup headed by Professor David Jones, and was originally founded as the Joint Research Council funded Bioinformatics Unit within the Department of Computer Science at University College London. Supports the following tools: Protein Structure Prediction Threading (THREADER) Ab initio folding simulations Secondary structure prediction (PSIPRED) Protein disorder prediction (DISOPRED) Protein domain prediction (DomPred) Database of protein disorder (DisoDB) Protein Sequence Analysis Protein function prediction (ffpred) Metsite: Metal binding residue prediction HSPred : Protein-protein interaction characterisation Amino acid substitution matrices Hidden Markov Models (collaboration with N. Goldman, Cambridge, & J. Thorne, NCSU) Genome Analysis Genomic fold recognition (GenTHREADER) Genome annotation using software agents Protein Structure Classification CATH (collaboration with J. Thornton & C. Orengo, UCL Biochemistry) Transmembrane Protein Modelling MEMSAT & MEMSATSVM Folding In Lipid Membranes (FILM) MEMPACK Biological Applications of Data-mining and Machine Learning Techniques Information extraction for biological research (BioRat) Microarray Analysis Data integration for microarray analysis Data visualization Systems Biology Systems biology applied to stem cells Legacy Services (to be retired shortly) Comparison of structure classifications (CATH/SCOP/FSSP) Genomic Threading Database (GTD)
View all literature mentionsA python software package that can identify nucleosome positions given histone-modification ChIP-seq or nucleosome sequencing at the nucleosome level.
View all literature mentionsSoftware tool which predicts possible impact of amino acid substitution on structure and function of human protein using straightforward physical and comparative considerations. PolyPhen-2 is new development of PolyPhen tool for annotating coding nonsynonymous SNPs.
View all literature mentionsSystem that classifies genes by their functions, using published scientific experimental evidence and evolutionary relationships to predict function even in absence of direct experimental evidence. Orthologs view is curated orthology relationships between genes for human, mouse, rat, fish, worm, and fly.
View all literature mentions