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Oral clefts are a major public health problem worldwide. The lip and palate form as a result of the cell proliferation (growth), apposition, and fusion of embryonic facial processes. This requires that the processes appear in the correct place, achieve the correct shape and size, and have no obstruction to fusion. Given the complex nature of this orofacial development, one can readily imagine a long list of potential mishaps. The inheritance patterns of oral clefts are not classically Mendelian, being more like polygenic quantitative traits. Indeed, mouse models suggest that differences in susceptibility to an environmental insult results from a genetically determined difference in normal oral development. That is, the growth of facial and palatal processes exhibit the continuous variation usually associated with the quantitative inheritance of phenotypes such as height and weight. Mouse models also suggest that an important epigenetic contribution to cleft etiology is variation in monoallelic gene expression. Understanding the interplay of genotype, epigenotype, and embryonic environment is critical to understanding the developmental mechanisms associated with normal and abnormal lip and palate ontogeny.
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