Beales P

Chapple JP

Copp A

Dollfus H

Eichers E

Eliot MM

Fisher S

Forge A

Henderson D

Hill J

Jagger D

Kai M

Katsanis N

Kemp D

Leitch C

Leroux M

Lupski J

May-Simera H

Munro P

Murdoch J

Phillips H

Ross A

Tada M

Tan P

Newcastle University E-Prints

Newcastle University e-prints  Date deposited:  11 July 2011 Version of file:  Published  Peer Review Status: Peer Reviewed Citation for published item: Ross A, May-Simera H, Eichers E, Kai M, Hill J, Jagger D, Leitch C, Chapple JP, Munro P, Fisher S, Tan P, Phillips H, Leroux M, Henderson D, Murdoch J, Copp A, Eliot MM, Lupski J, Kemp D, Dollfus H, Tada M, Katsanis N, Forge A, Beales P. Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates. In: Genetics Research: 16th Mammalian Genetics and Development Workshop of the Genetics Society. 2006, London, UK: Cambridge University Press.  Further information on publisher website: http://journals.cambridge.org/action/displayJournal?jid=GRH Publishers copyright statement: © Cambridge University Press 2006. This paper is published by Cambridge University Press, and is available with access permissions, from the DOI below: http://dx.doi.org/10.1017/S0016672306008317  Always use the definitive version when citing.  Use Policy: The full-text may be used and/or reproduced and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not for profit purposes provided that: • A full bibliographic reference is made to the original source • A link is made to the metadata record in Newcastle E-prints • The full text is not changed in any way. The full-text must not be sold in any format or medium without the formal permission of the copyright holders.    Robinson Library, Newcastle University, Newcastle upon Tyne, NE1 7RU.   Tel. 0191 222 6000 two patients with spina bifida carry rare structuralchromosomal abnormalities. The approach of usingchromosomal rearrangements in key patients maybe an important first step towards the identificationof a disease gene since a chromosomal rearrange-ment may pinpoint the localization of a disease gene.We hypothesize that the chromosomal rearrange-ments in the two patients with spina bifida mayresult in a phenotype because of the disruption ofa functional gene or genes. In order to positionallyclone candidate genes for neural tube defects, a de-tailed mapping of the chromosomal abnormalitiesis in progress. Candidate genes are analysed forexpression patterns and for mutations in patientDNA. Also, we have initiated array-based CGH(comparative genomic hybridization) analysis inpatients with MMC to screen for minor chromosomalabnormalities.Disruption of Bardet-Biedl syndrome ciliary proteinsperturbs planar cell polarity in vertebratesALISON ROSS1, HELEN MAY-SIMERA1, ERICAEICHERS2, MASATAKE KAI3, JOSEPHINEHILL1, DANIEL JAGGER4, CARMEN LEITCH5,J. PAUL CHAPPLE6, PETER MUNRO6,SHANNON FISHER5, PERCILIZ TAN5, HELENPHILLIPS7, MICHEL LEROUX8, DEBORAHHENDERSON7, JENNIFER MURDOCH9,ANDREW COPP10, MARIE-MADELEINEELIOT11, JAMES LUPSKI2, DAVID KEMP4,HÉLÈNE DOLLFUS12, MASAZUMI TADA3,NICHOLASKATSANIS5, ANDREWFORGE4 andPHILIP BEALES11Molecular Medicine Unit, Institute of Child Health,UCL, London WC1N 1EH, UK; 2Department ofMolecular and Human Genetics, Baylor College ofMedicine, Houston, TX 77030, USA; 3Departmentof Anatomy and Developmental Biology, UCL, LondonWC1E 6BT, UK; 4Centre for Auditory Research, TheEar Institute, UCL, London, UK; 5Institute of GeneticMedicine, Wilmer Eye Institute, Johns HopkinsUniversity, Baltimore, MD 21287, USA; 6Instituteof Ophthalmology, UCL, London EC1V 9EL, UK;7Institute of Human Genetics, University of Newcastleupon Tyne, Newcastle upon Tyne, UK; 8Departmentof Molecular Biology and Biochemistry, Simon FraserUniversity, Burnaby, BC, Canada V5 1S6; 9MRCMammalian Genetics Unit, MRC Harwell, Oxford-shire OX11 0RD, UK; 10Neural Development Unit,Institute of Child Health, UCL, London WC1N 1EH,UK; 11Service d’ORL, Hôpitaux Universitaires deStrasbourg, Strasbourg, France; 12Service de Génét-ique Médicale, Hôpitaux Universitaires de Strasbourg;Laboratoire de Génétique Médicale, Faculté de Méde-cine, Université Louis Pasteur de Strasbourg, FranceThe evolutionarily conserved planar cell polarity(PCP) pathway (or non-canonical Wnt pathway)drives several important cellular processes, includingepithelial cell polarization, cell migration and mitoticspindle orientation. In vertebrates, PCP genes play avital role in polarized convergent extension move-ments during gastrulation and neurulation. Here,we show that mice with mutations in genes involvedin Bardet-Biedl syndrome (BBS), a disorder associ-ated with ciliary dysfunction, share phenotypeswith PCP mutants including open eyelids, neural tubedefects and disrupted cochlear stereociliary bundles.Furthermore, we demonstrate genetic interactionsbetween BBS genes and a PCP gene, Vangl2, in bothmouse and zebrafish; in the latter we show that theaugmented phenotype results from enhanced defec-tive convergent extension movements. We also showthat Vangl2 localizes to the basal body and axonemeof ciliated cells, a pattern reminiscent of the BBSproteins. These data suggest, for the first time, thatcilia are intrinsically involved in PCP processes.This work is supported by grants from the Wellcome Trust(A.J.R., J.H., A.J.C.), Medical Research Council (H.M.S.& M.T.), Birth Defects Foundation (J.H.), DefeatingDeafness (A.F.), the National Institute of Child Health andDevelopment and National Institute of Diabetes, Digestiveand Kidney Disorders, NIH (N.K.), British HeartFoundation (D.H.). M.R.L. acknowledges funding fromHSFBC&Y and CIHR (CBM134736), and scholarshipsfrom MSFHR and CIHR. P.L.B. is a Wellcome TrustSenior Research Fellow.Mutations in the endosomal ESCRTIII complexsubunit CHMP2B in frontotemporal dementiaGAIA SKIBINSKI, NICK PARKINSON,ELIZABETH FISHER, JOHN COLLINGE and theFREJA CONSORTIUMMRC Prion Unit, Institute of Neurology, UCL, QueenSquare, London WC1N 3BG, UKFrontotemporal dementia (FTD) is a common causeof early-onset progressive dementia characterizedby personality and/or language changes. FTD locihave already been identified on chromosome 17 andchromosome 9. In addition an autosomal dominantform of FTD in a Danish family has previously beenlinked to the pericentromeric region of chromosome 3(FTD3). This project aimed to identify the mutantgene causing FTD3. Haplotype analysis narrowedthe disease locus to a physical distance of 15.5 Mbbetween flanking markers, D3S3581 and D3S3690.Sequence analysis of candidate genes identified amutation in the 3k acceptor splice site of exon 6 inCHMP2B that segregated with only affected FTD3family members. This mutation disrupts RNAAbstracts of papers 75

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Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates

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Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates

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