The current proposal seeks activation ofthe ROO phase of a K99/R00 award (1K99DE018085). The Pl, Dr. Manika Govil, is a statistical geneticist at the University of Pittsburgh School of Dental Medicine's Center for Craniofacial and Dental Genetics. She has fulfilled the career development aims planned for the K99 phase and is ready to move to an independent position in the ROO phase. The institutional support and environment have been instrumental for the Pi's achievements. A goal of the K99 phase of the Pi's work was to gain fundamental knowledge of craniofacial and dental genetic disorders, with special emphasis on understanding the etiology, epidemiology, and phenotypes of CL/P. A deeper understanding of CL/P and other complex genetic traits is critical to the development of methods with computationally feasible implementations that will be capable of modeling the expected heterogeneity in the data to identify multigenic causes. Her long-term goal is to become an independent, interdisciplinary research scientist with a funded research program that will bring together expertise in statistics and computer science to advance our understanding of complex traits like craniofacial and dental genetic disorders. To achieve these goals. Dr. Govil has completed training under Drs. Mary Marazita and Veronica Vieland during the K99-phase of her grant. Dr. Marazita is the PI on several craniofacial and dental genetic grants, and has expertise in orofacial research. Dr. Viejand is the PI on grants relating to methods development for complex traits, as well as grants for the analysis of complex traits like autism and CL/P. The experimental focus ofthis proposal is on the development and implementation of computationally feasible statistical genetic methods, in particular, extensions to the posterior probability of linkage (PPL), a model-free likelihood-based class of methods;comparison ofthese methods to other existing statistical approaches, and their application to the analysis of complex craniofacial and dental genetic disorders like cleft lip with or without cleft palate and oral health disparity.

Public Health Relevance

Complex genetic traits including craniofacial and dental genetic disorders like CL/P constitute a significant public health burden. The aim ofthis project is to further our understanding of CL/P and other complex traits by developing, implementing computationally, and applying in analyses, statistical methods that are capable of modelling genetic factors, with/out possible environmental factors, that may be responsible for such traits.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Transition Award (R00)
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Special Emphasis Panel (NSS)
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Harris, Emily L
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University of Pittsburgh
Schools of Dentistry
United States
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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
Letra, Ariadne; Menezes, Renato; Cooper, Margaret E et al. (2011) CRISPLD2 variants including a C471T silent mutation may contribute to nonsyndromic cleft lip with or without cleft palate. Cleft Palate Craniofac J 48:363-70
Letra, A; Menezes, R; Fonseca, R F et al. (2010) Novel cleft susceptibility genes in chromosome 6q. J Dent Res 89:927-32
Letra, Ariadne; Menezes, Renato; Govil, Manika et al. (2010) Follow-up association studies of chromosome region 9q and nonsyndromic cleft lip/palate. Am J Med Genet A 152A:1701-10
de Carvalho, Flavia M; Tinoco, Eduardo M B; Govil, Manika et al. (2009) Aggressive periodontitis is likely influenced by a few small effect genes. J Clin Periodontol 36:468-73
Marazita, Mary L; Lidral, Andrew C; Murray, Jeffrey C et al. (2009) Genome scan, fine-mapping, and candidate gene analysis of non-syndromic cleft lip with or without cleft palate reveals phenotype-specific differences in linkage and association results. Hum Hered 68:151-70