Related Content
Search Google Scholar for:
More Information
Related Jobs from ScienceCareers
|
Originally published in Science Express on 3 November 2005
Science 18 November 2005:
Vol. 310. no. 5751, pp. 1184 - 1187
DOI: 10.1126/science.1116142
|
|
Reports
GTF2IRD1 in Craniofacial Development of Humans and Mice
May Tassabehji,1*
Peter Hammond,2
Annette Karmiloff-Smith,3
Pamela Thompson,1
Snorri S. Thorgeirsson,4
Marian E. Durkin,4
Nicholas C. Popescu,4
Timothy Hutton,2
Kay Metcalfe,1
Agnes Rucka,1
Helen Stewart,5
Andrew P. Read,1
Mark Maconochie,6
Dian Donnai1
Craniofacial abnormalities account for about one-third of all human congenital defects, but our understanding of the genetic mechanisms governing craniofacial development is incomplete. We show that GTF2IRD1 is a genetic determinant of mammalian craniofacial and cognitive development, and we implicate another member of the TFII-I transcription factor family, GTF2I, in both aspects. Gtf2ird1-null mice exhibit phenotypic abnormalities reminiscent of the human microdeletion disorder Williams-Beuren syndrome (WBS); craniofacial imaging reveals abnormalities in both skull and jaws that may arise through misregulation of goosecoid, a downstream target of Gtf2ird1. In humans, a rare WBS individual with an atypical deletion, including GTF2IRD1, shows facial dysmorphism and cognitive deficits that differ from those of classic WBS cases. We propose a mechanism of cumulative dosage effects of duplicated and diverged genes applicable to other human chromosomal disorders.
1 Academic Unit of Medical Genetics, University of Manchester, St. Mary's Hospital, Manchester M13 9PL, UK.
2 Eastman Dental Institute, University College London, London WC1E 6BT, UK.
3 Institute of Child Health, University College London, London WC1E 6BT, UK.
4 National Cancer Institute, Bethesda, MD 20892, USA.
5 Churchill Hospital, Oxford OX3 7LJ, UK.
6 School of Life Sciences, University of Sussex, Brighton BN1 9RH, UK.
* To whom correspondence should be addressed. E-mail: m.tassabehji{at}manchester.ac.uk
Read the Full Text
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
- Identification of the TFII-I family target genes in the vertebrate genome.
- N.-O. Chimge, A. V. Makeyev, F. H. Ruddle, and D. Bayarsaihan (2008)
PNAS
105, 9006-9010
| Abstract »
| Full Text »
| PDF »
- Inhibition of neural crest migration underlies craniofacial dysmorphology and Hirschsprung's disease in Bardet-Biedl syndrome.
- J. L. Tobin, M. Di Franco, E. Eichers, H. May-Simera, M. Garcia, J. Yan, R. Quinlan, M. J. Justice, R. C. Hennekam, J. Briscoe, et al. (2008)
PNAS
105, 6714-6719
| Abstract »
| Full Text »
| PDF »
- Determination and Functional Analysis of the Consensus Binding Site for TFII-I Family Member BEN, Implicated in Williams-Beuren Syndrome.
- M. B. Lazebnik, M. I. Tussie-Luna, and A. L. Roy (2008)
J. Biol. Chem.
283, 11078-11082
| Abstract »
| Full Text »
| PDF »
- Autism, language delay and mental retardation in a patient with 7q11 duplication.
- C Depienne, D Heron, C Betancur, B Benyahia, O Trouillard, D Bouteiller, A Verloes, E LeGuern, M Leboyer, and A Brice (2007)
J. Med. Genet.
44, 452-458
| Abstract »
| Full Text »
| PDF »
- Genetic aspects of birth defects: new understandings of old problems.
- K. R Prescott and A. O M Wilkie (2007)
Arch. Dis. Child. Fetal Neonatal Ed.
92, F308-F314
| Abstract »
| Full Text »
| PDF »
- An atypical deletion of the Williams-Beuren syndrome interval implicates genes associated with defective visuospatial processing and autism.
- L. Edelmann, A. Prosnitz, S. Pardo, J. Bhatt, N. Cohen, T. Lauriat, L. Ouchanov, P. J Gonzalez, E. R Manghi, P. Bondy, et al. (2007)
J. Med. Genet.
44, 136-143
| Abstract »
| Full Text »
| PDF »
- New techniques to understand chromosome dosage: mouse models of aneuploidy.
- V. L.J. Tybulewicz and E. M.C. Fisher (2006)
Hum. Mol. Genet.
15, R103-R109
| Abstract »
| Full Text »
| PDF »
|
|
