Presentation Blocks: 03-22-2018 - Thursday - 03:45 PM - 05:00 PM

Title: Identifying DACH1 Variants Contributing to Orofacial Clefts in African Populations


James Park (Presenter)
University of Iowa College of Dentistry

Azeez Butali, University of Iowa
TAMARA BUSCH, University of Iowa
Shaan Desai, University of Iowa College of Dentistry
Ada ToraƱo, University of Puerto Rico
Carolina Bello, University of Puerto Rico
Cynthia Lo, University of Iowa
Muawia Mohamed, University of Iowa


Objectives: Orofacial clefts are the most common craniofacial malformation in humans, occurring in about 1 out of every 700 births worldwide. The causes of orofacial clefts are complex, with race, ethnicity, geographic locations, environment factors, and socioeconomic status all contribute to the incidence of this disease. The goal of this project was to identify variants in the Dachshund Family Transcription Factor 1(DACH1) gene that could contribute to the development of nonsyndromic orofacial clefts.

Methods: The DACH1 gene was recently identified through the first African Clefts Genome-Wide Association Study (GWAS) as highly associated with individuals with nonsyndromic orofacial clefts. We preformed Sanger sequencing of the DACH1 gene in 288 individuals from Ghana, Nigeria, or Ethiopia with nonsydromic cleft lip and palate and used SIFT, PolyPhen, and HOPE bioinformatic tools to predict effects of variant

Results: We found 1 novel missense variation (p.Gly739Ser) in 2 individuals from Ghana and Nigeria. It was predicted as tolerated (low confidence) and benign by SIFT and PolyPhen bioinformatic tools, respectively. This missense variation changes the protein sequence of the DACH1 gene and, according to HOPE bioinformatic tool, could change the folding and function of the protein by exchanging the smaller amino acid Glycine with the larger Serine.

Conclusions: We have identified a novel variant, but have not yet fully explained the biology of that variant, which requires further research. We hope that our finding will lead us to a more complete understanding of the complex etiology of orofacial clefts and give us the tools to reduce the negative psycho-social impact of orofacial clefts on individuals affected and their families.