Cleft lip and cleft palate are common birth defects affecting 1-2/1000 live births. It is apparent that genetic factors contribute significantly to their etiology. Most orofacial clefts are non- syndromic, isolated effects, which can be separated into two different phenotypes: (1) cleft lip with or without cleft palate (CL/P) and 2) cleft palate only (CPO). Both are genetically complex traits, which has limited the ability to identify disease loci or genes. Previous effects to determine the genetic etiology for non-syndromic clefts have relied on candidate gene approaches with most studies focused on CL/P. The overall objective of this and future projects is to identify disease loci and genes involved in non-syndromic CPO by employing new linkage strategies to study affected relative pairs and extended pedigrees. These approaches, which have yet been applied to CPO, are very powerful in that no prior knowledge about the involved biological processes or inheritance pattern is needed.
The specific aim of this project is to ascertain 150 families with multiple members affected with CPO from the Shanghai region of China. An additional 100 CPO patients will be ascertained along with their parents for use in linkage disequilibrium analyses. This will be performed in collaboration with Dr. You-e Liu of the Zhabei Eye Hospital, Shanghai and Dr. Mary Marazita of the Cleft Palate Center, Pittsburgh, who have collaborated since Cleft Palate Clinic at the University of Pittsburgh Cleft Palate-Craniofacial Center to add to the 45 families already recruited through the efforts of there collaborative investigators. The scope of this project will be to evaluate candidate genes for CPO using both linkage and linkage disequilibrium analyses. The population of Shanghai, China is relatively homogeneous, which a unique quality that increases the power to map a disease loci and also facilitate the transition to physical mapping and gene identification. The strength of this study is the relatively large numbers of affected relative pairs that can be ascertained at multiple sites, thus increasing the overall power for the study to detect loci of even modest effect. It will be through projects such as this one, in which collaborations with researchers world wide have been established to apply a combination of genetic strategies, that disease loci for CPO will be identified. Ultimately, this will further the knowledge of normal and abnormal craniofacial development, such that therapies to prevent CPO can be developed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Comprehensive Center (P60)
Project #
3P60DE013076-01S1
Application #
6300920
Study Section
Project Start
1999-08-01
Project End
2000-07-31
Budget Start
Budget End
Support Year
1
Fiscal Year
2000
Total Cost
$135,447
Indirect Cost
Name
University of Iowa
Department
Type
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Haworth, Simon; Shungin, Dmitry; van der Tas, Justin T et al. (2018) Consortium-based genome-wide meta-analysis for childhood dental caries traits. Hum Mol Genet 27:3113-3127
Govil, Manika; Mukhopadhyay, Nandita; Weeks, Daniel E et al. (2018) Novel caries loci in children and adults implicated by genome-wide analysis of families. BMC Oral Health 18:98
Yang, Jie; Zhu, Wei; Chen, Jiansong et al. (2014) Genome-wide two-marker linkage disequilibrium mapping of quantitative trait loci. BMC Genet 15:20
Beaty, T H; Taub, M A; Scott, A F et al. (2013) Confirming genes influencing risk to cleft lip with/without cleft palate in a case-parent trio study. Hum Genet 132:771-81
Skare, Oivind; Jugessur, Astanand; Lie, Rolv Terje et al. (2012) Application of a novel hybrid study design to explore gene-environment interactions in orofacial clefts. Ann Hum Genet 76:221-36
Wehby, G L; Tyler, M C; Lindgren, S et al. (2012) Oral clefts and behavioral health of young children. Oral Dis 18:74-84
Shaffer, J R; Wang, X; Feingold, E et al. (2011) Genome-wide association scan for childhood caries implicates novel genes. J Dent Res 90:1457-62
Schneider, Galen B; Zaharias, Rebecca; Seabold, Denise et al. (2011) Integrin-associated tyrosine kinase FAK affects Cbfa1 expression. J Orthop Res 29:1443-7
Larjava, H; Koivisto, L; Häkkinen, L et al. (2011) Epithelial integrins with special reference to oral epithelia. J Dent Res 90:1367-76
Jugessur, Astanand; Shi, Min; Gjessing, Håkon Kristian et al. (2010) Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia. PLoS One 5:e11493

Showing the most recent 10 out of 83 publications