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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum
Nature Genetics, Volume 43, No. 3, Year 2011
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Description
Ciliary dysfunction leads to a broad range of overlapping phenotypes, collectively termed ciliopathies. This grouping is underscored by genetic overlap, where causal genes can also contribute modifier alleles to clinically distinct disorders. Here we show that mutations in TTC21B, which encodes the retrograde intraflagellar transport protein IFT139, cause both isolated nephronophthisis and syndromic Jeune asphyxiating thoracic dystrophy. Moreover, although resequencing of TTC21B in a large, clinically diverse ciliopathy cohort and matched controls showed a similar frequency of rare changes, in vivo and in vitro evaluations showed a significant enrichment of pathogenic alleles in cases (P < 0.003), suggesting that TTC21B contributes pathogenic alleles to ∼5% of ciliopathy cases. Our data illustrate how genetic lesions can be both causally associated with diverse ciliopathies and interact in trans with other disease-causing genes and highlight how saturated resequencing followed by functional analysis of all variants informs the genetic architecture of inherited disorders. © 2011 Nature America, Inc. All rights reserved.
Authors & Co-Authors
Davis, Erica E.
United States, Durham
Duke University Medical Center
Zhang, Qi
United States, Philadelphia
University of Pennsylvania Perelman School of Medicine
Liu, Qin
United States, Philadelphia
University of Pennsylvania Perelman School of Medicine
Diplas, Bill H.
United States, Durham
Duke University Medical Center
Davey, Lisa M.
United States, Durham
Duke University Medical Center
Hartley, Jane
United Kingdom, Birmingham
University of Birmingham
Stoetzel, Corinne
France, Strasbourg
Université de Strasbourg
Szymanska, Katarzyna
United Kingdom, Leeds
St James's University Hospital
Ramaswami, Gokul
United States, Ann Arbor
University of Michigan, Ann Arbor
Logan, Clare V.
United Kingdom, Leeds
St James's University Hospital
Muzny, Donna Marie
United States, Houston
Baylor College of Medicine
Young, Alice C.
United States, Bethesda
National Human Genome Research Institute Nhgri
Wheeler, David A.
United States, Houston
Baylor College of Medicine
Cruz, Pedro
United States, Bethesda
National Human Genome Research Institute Nhgri
Morgan, Margaret B.
United States, Houston
Baylor College of Medicine
Lewis, Lora R.
United States, Houston
Baylor College of Medicine
Cherukuri, Praveen
United States, Bethesda
National Human Genome Research Institute Nhgri
Maskeri, Baishali
United States, Bethesda
National Human Genome Research Institute Nhgri
Hansen, Nancy F.
United States, Bethesda
National Human Genome Research Institute Nhgri
Mullikin, James C.
United States, Bethesda
National Human Genome Research Institute Nhgri
Blakesley, Robert W.
United States, Bethesda
National Human Genome Research Institute Nhgri
Bouffard, Gerard G.
United States, Bethesda
National Human Genome Research Institute Nhgri
Gyapay, Gábor
France, Evry
Genoscope - Centre National de Séquençage
Rieger, Susanne
Germany, Heidelberg
Universitätsklinikum Heidelberg
Tönshoff, Burkhard
Germany, Heidelberg
Universitätsklinikum Heidelberg
Kern, Ilse
Switzerland, Geneva
Hôpitaux Universitaires de Genève
Soliman Elshakhs, Neveen A.
Egypt, Cairo
Faculty of Medicine
Neuhaus, Thomas J.
Switzerland, Zurich
Kinderspital Zürich
Swoboda, Kathryn J.
United States, Salt Lake City
University of Utah School of Medicine
Kayserili, Hülya U.
Turkey, Istanbul
İstanbul Tıp Fakültesi
Gallagher, Tomas E.
United States, Honolulu
University of Hawaiʻi at Mānoa
Lewis, R. A.
United States, Houston
Baylor College of Medicine
Bergmann, Carsten
Germany, Ingelheim am Rhein
Center for Human Genetics
Germany, Aachen
Rheinisch-westfälische Technische Hochschule Aachen
Otto, Edgar A.
United States, Ann Arbor
University of Michigan, Ann Arbor
Saunier, Sophie
France, Paris
Inserm
Scambler, Peter James
United Kingdom, London
Ucl Great Ormond Street Institute of Child Health
Beales, Philip L.Philip L.
United Kingdom, London
Ucl Great Ormond Street Institute of Child Health
Gleeson, Joseph G.
United States, La Jolla
Department of Neurosciences
Mäher, Eamonn Richard
United Kingdom, Birmingham
University of Birmingham
Attié-Bitach, Tania
France, Paris
Hôpital Necker Enfants Malades
Dollfus, Hélène J.
France, Strasbourg
Université de Strasbourg
Johnson, Colin A.
United Kingdom, Leeds
St James's University Hospital
Green, Eric D.
United States, Bethesda
National Human Genome Research Institute Nhgri
Gibbs, Richard A.L.
United States, Houston
Baylor College of Medicine
Hildebrandt, Friedhelm
United States, Ann Arbor
University of Michigan, Ann Arbor
Pierce, Eric A.
United States, Philadelphia
University of Pennsylvania Perelman School of Medicine
Katsanis, Nicholas
United States, Durham
Duke University Medical Center
United States, Baltimore
Wilmer Eye Institute
Statistics
Citations: 348
Authors: 47
Affiliations: 23
Identifiers
Doi:
10.1038/ng.756
ISSN:
10614036
e-ISSN:
15461718
Research Areas
Disability
Genetics And Genomics
Study Design
Cohort Study