Nonsyndromic cleft lip with or without cleft palate (CUP) is a disease of complex etiology. Although significant work has been done, with many important findings, the genetics of CUP is poorly understood. Herein we present a plan for a novel set of analyses on a CUP pedigree sample of unprecedented size and an independent set of 1000 CUP trios. Importantly, this dataset has CIDR genome scan data available, has been accepted for an Illumina fine-mapping project with CIDR and has many candidate loci already genotyped. Our analysis plan will consist of three distinct approaches to CUP gene discovery. First, we will use a non-parametric linkage approaches to detecting gene-gene interaction, incorporating either a previous linkage finding or candidate gene marker in the model. Second, we will use association approaches to detect interaction at a set of candidate genes. Lastly, we will use empirical information to inform a novel approach to linkage analysis incorporating a parameter representing diagnostic uncertainty. Overall, the proposed analytical approaches applied in this large dataset will shed significant light on the contribution of specific genes, and their interactions, to CUP. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Small Research Grants (R03)
Project #
1R03DE016632-01A2
Application #
7196889
Study Section
Special Emphasis Panel (ZDE1-PZ (72))
Program Officer
Harris, Emily L
Project Start
2007-08-01
Project End
2009-07-31
Budget Start
2007-08-01
Budget End
2008-07-31
Support Year
1
Fiscal Year
2007
Total Cost
$149,000
Indirect Cost
Name
Virginia Commonwealth University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298