Orofacial clefts are a major public health problem, affecting one in every 500-1000 births worldwide. There has been substantial recent progress by our group and others in identifying genetic loci for cleft lip with or without cleft palate (CUP), confirming the suspected complexity in the genetic etiology of CUP. As the genetic factors contributing to CL/P emerge, it is essential to identify the phenotypic characteristics attributable to each gene in order to translate the emerging research results into clinical practice. The primary goal of this study is to identify the phenotypes that are segregating at a genetic level in cleft' families, thereby extending the clinical phenotypic spectrum of CUP and identifying apparently unaffected individuals who are likely to be carrying cleft genes (e.g. individuals with sub-clinical phenotypic expression). Upon meeting this goal, recurrence risk calculation and genetic counseling for this common birth defect will be vastly improved. The specific features that will be investigated include: handedness, craniofacial measurements, asymmetry (based on dermatoglyphic patterns and craniofacial measurements), velopharyngeal competence (by perceptual screening) and anatomy of the orbicularis oris muscle. In order to succeed in characterizing the individual genes involved in each CL/P phenotype, large numbers of families are necessary for statistical power. Therefore, the current grant proposal is an international planning grant with the aim of ascertaining the large numbers of families necessary for the study aims. Three populations are targeted: Guatemala, Spain, and Hungary, with preliminary contacts made for each population. During the two years of the planning grant, we will confirm the necessary collaborations and logistics for carrying out the research protocol in each study population, will have planning meetings at the University of Pittsburgh, will carry out a minimum of one trip to each population in order to collect pilot data, will have planning meetings at the University of Pittsburgh, will use the pilot data to develop the research plan (e.g. power studies and sample size targets, research protocol and instruments), and will prepare the final research plan and submit a grant proposal to carry out the research project. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DE016930-01A1
Application #
7091036
Study Section
Special Emphasis Panel (ZDE1-SK (26))
Program Officer
Harris, Emily L
Project Start
2006-07-01
Project End
2008-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
1
Fiscal Year
2006
Total Cost
$148,500
Indirect Cost
Name
University of Pittsburgh
Department
Dentistry
Type
Schools of Dentistry
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Howe, Laurence J; Lee, Myoung Keun; Sharp, Gemma C et al. (2018) Investigating the shared genetics of non-syndromic cleft lip/palate and facial morphology. PLoS Genet 14:e1007501
Shaffer, John R; LeClair, Jessica; Carlson, Jenna C et al. (2018) Association of low-frequency genetic variants in regulatory regions with nonsyndromic orofacial clefts. Am J Med Genet A :
Carlson, Jenna C; Nidey, Nichole L; Butali, Azeez et al. (2018) Genome-wide interaction studies identify sex-specific risk alleles for nonsyndromic orofacial clefts. Genet Epidemiol 42:664-672
Chernus, Jonathan; Roosenboom, Jasmien; Ford, Matthew et al. (2018) GWAS reveals loci associated with velopharyngeal dysfunction. Sci Rep 8:8470
Carlson, Jenna C; Taub, Margaret A; Feingold, Eleanor et al. (2017) Identifying Genetic Sources of Phenotypic Heterogeneity in Orofacial Clefts by Targeted Sequencing. Birth Defects Res 109:1030-1038
Carlson, Jenna C; Taub, Margaret A; Feingold, Eleanor et al. (2017) Identifying Genetic Sources of Phenotypic Heterogeneity in Orofacial Clefts by Targeted Sequencing. Birth Defects Res :
Leslie, Elizabeth J; Carlson, Jenna C; Cooper, Margaret E et al. (2017) Exploring Subclinical Phenotypic Features in Twin Pairs Discordant for Cleft Lip and Palate. Cleft Palate Craniofac J 54:90-93
Liu, Dongjing; Wang, Hong; Schwender, Holger et al. (2017) Gene-gene interaction of single nucleotide polymorphisms in 16p13.3 may contribute to the risk of non-syndromic cleft lip with or without cleft palate in Chinese case-parent trios. Am J Med Genet A 173:1489-1494
Leslie, Elizabeth J; Carlson, Jenna C; Shaffer, John R et al. (2017) Association studies of low-frequency coding variants in nonsyndromic cleft lip with or without cleft palate. Am J Med Genet A 173:1531-1538
Xiao, Yanzi; Taub, Margaret A; Ruczinski, Ingo et al. (2017) Evidence for SNP-SNP interaction identified through targeted sequencing of cleft case-parent trios. Genet Epidemiol 41:244-250

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