Candidate: Dr Azeez Butali is a Postdoctoral Research Scholar at the Carver College of Medicine, the University of Iowa. His primary research focus is on the genetics and epidemiology of complex craniofacial disorders including orofacial clefts. His short-term career goals are to deepen his knowledge of the genetics of complex craniofacial traits such as orofacial clefts and expand current understanding of molecular techniques to evaluate these traits. His long-term goals are to become a funded independent scientist in the fields of craniofacial genetics and dentistry as tenure-track faculty at a University. His research plan is innovative in using molecular genetic techniques to investigate the genetic etiology of orofacial clefts in populations of African ancestry in other to understand these complex traits. This research will utilize the samples obtained through the International Genetic Epidemiology Consortium at the Craniofacial Research Center (CARC), University of Iowa. This research has the potential of identifying new biological pathways involved in orofacial clefts and will provide new information on correlation between clinical cleft sub-phenotypes and significant SNPs arising from genome wide association studies. It also has the potential of having direct clinical impact on the management of orofacial clefts. Mentors and Consultants: Dr. Jeffrey Murray will serve as primary mentor on this award. He is a well-funded full professor at the University of Iowa with 25 years of experience in training successful graduate and postdoctoral students. Dr. Andrew Lidral, an expert in the field of craniofacial genetics, will serve as co-mentor to this award. Drs. Mary Marazita and Adebowale Adeyemo will serve as consultants on this project by providing clinical and statistical genetic expertise. Drs. Peter Mossey, Paul Romitti and George Wehby will serve as external advisory members and will consult with, advice and evaluate the progress of Dr. Butali throughout the award period and they have complementary expertise in the craniofacial genetics, epidemiology, dentistry and genomic analysis. Environment: The University of Iowa has an established reputation for the successful training of graduate and postdoctoral students, particularly in research and clinical areas. The University offers a range of learning and development seminars as well as other programs focused on career development and advancement, and particularly benefits from training opportunities deriving from its ICTS (Institute for Clinical and Translational Sciences) support by a CTSA award. Career Development Plan: Dr. Butali plans to meet regularly with his mentors, consultants and external advisory members to gain the knowledge necessary to obtain his career and research goals as well as attending tutorials, courses, seminars and relevant conferences. Research Study: The focus of this study is to understand the complex genetic etiology of orofacial clefts by determining the genetic variations that contributes to it in homogenous African populations and relate these findings to prevention and clinical management of the disease.

Public Health Relevance

Understanding the etiology of complex genetic diseases can only be accomplished by studying different population groups with variety of environmental, phenotypic and genetic variables. The focus of this work will be to use the International collaborative network at Craniofacial Research Center (CARC), University of Iowa to obtain samples from African populations in Nigeria and Ethiopia and admixed African-American populations in the U.S.A and as model for studying genetic variations that contribute to the etiology of orofacial clefts in diverse populations. This research will aid in our understanding of the etiology of these complex traits while identifying key genetic and environmental pathways that will inform strategies towards improved clinical care of individuals and ultimately prevention.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Career Transition Award (K99)
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NIDCR Special Grants Review Committee (DSR)
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Frieden, Leslie A
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University of Iowa
Schools of Medicine
Iowa City
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Eshete, M A; Liu, H; Li, M et al. (2018) Loss-of-Function GRHL3 Variants Detected in African Patients with Isolated Cleft Palate. J Dent Res 97:41-48
Oseni, Ganiyu O; Jain, Deepti; Mossey, Peter A et al. (2018) Identification of paternal uniparental disomy on chromosome 22 and a de novo deletion on chromosome 18 in individuals with orofacial clefts. Mol Genet Genomic Med 6:924-932
Gowans, Lord Jephthah Joojo; Busch, Tamara D; Mossey, Peter A et al. (2017) The prevalence, penetrance, and expressivity of etiologicIRF6variants in orofacial clefts patients from sub-Saharan Africa. Mol Genet Genomic Med 5:164-171
Liu, Huan; Busch, Tamara; Eliason, Steven et al. (2017) Exome sequencing provides additional evidence for the involvement of ARHGAP29 in Mendelian orofacial clefting and extends the phenotypic spectrum to isolated cleft palate. Birth Defects Res 109:27-37
Adeola, Henry A; Soyele, Olujide O; Adefuye, Anthonio O et al. (2017) Omics-based molecular techniques in oral pathology centred cancer: prospect and challenges in Africa. Cancer Cell Int 17:61
Adeyemo, Wasiu Lanre; James, Olutayo; Butali, Azeez (2016) Cleft lip and palate: Parental experiences of stigma, discrimination, and social/structural inequalities. Ann Maxillofac Surg 6:195-203
Awoyale, T; Onajole, A T; Ogunnowo, B E et al. (2016) Quality of life of family caregivers of children with orofacial clefts in Nigeria: a mixed-method study. Oral Dis 22:116-22
Leslie, Elizabeth J; Carlson, Jenna C; Shaffer, John R et al. (2016) A multi-ethnic genome-wide association study identifies novel loci for non-syndromic cleft lip with or without cleft palate on 2p24.2, 17q23 and 19q13. Hum Mol Genet 25:2862-2872
Liu, Huan; Leslie, Elizabeth J; Jia, Zhonglin et al. (2016) Irf6 directly regulates Klf17 in zebrafish periderm and Klf4 in murine oral epithelium, and dominant-negative KLF4 variants are present in patients with cleft lip and palate. Hum Mol Genet 25:766-76
Jia, Zhonglin; Leslie, Elizabeth J; Cooper, Margaret E et al. (2015) Replication of 13q31.1 association in nonsyndromic cleft lip with cleft palate in Europeans. Am J Med Genet A 167A:1054-1060

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