This application is in response to PAR-04-091. This goal of the project is to apply novel data analytic methods to an existing data set, in order to localize all genes of measurable effect underlying nonsyndromic cleft lip with or without cleft palate (CUP). CUP is a major structural birth defect, representing a significant public health burden. While a genetic role in etiology is certain, genome-wide linkage studies have been inconclusive. In an effort to achieve a comprehensive overview of the genetics of human CUP, we have undertaken the largest gene-mapping study to date by pooling together multiple independently collected sets of families manifesting CUP, drawn from 7 populations around the world. The Center for Inherited Disease Research has completed genotyping for an (approximate) 10 cM genome-screen on all families, and is currently completing genotyping based on a custom 1500 SNP panel. We now propose to analyze these data using a novel Bayesian approach to linkage and linkage disequilibrium mapping, specifically designed for the analysis of heterogeneous conditions based on multiple, genetically diverse samples. We will also conduct systematic comparisons of the performance of the Bayesian method with other commonly used statistics. This project will thus provide a comprehensive assessment, in both genomic and geographical terms, of the genetic architecture of CUP. It will also result in a set of recommendations regarding optimal data analytic methods for gene mapping studies of complex disorders based on multi-site designs . ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Small Research Grants (R03)
Project #
5R03DE017167-03
Application #
7231479
Study Section
Special Emphasis Panel (ZDE1-RR (81))
Program Officer
Mcinnes, Pamela M
Project Start
2006-07-01
Project End
2008-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
3
Fiscal Year
2007
Total Cost
$139,824
Indirect Cost
Name
Nationwide Children's Hospital
Department
Type
DUNS #
147212963
City
Columbus
State
OH
Country
United States
Zip Code
43205
Govil, M; Vieland, V J (2008) Practical considerations for dividing data into subsets prior to PPL analysis. Hum Hered 66:223-37
Govil, Manika; Segre, Alberto M; Vieland, Veronica J (2008) MLIP: using multiple processors to compute the posterior probability of linkage. BMC Bioinformatics 9 Suppl 6:S2