title: Evaluating rare coding variants as contributing causes to non-syndromic cleft lip and palate.
abstract: Rare coding variants are a current focus in studies of complex disease. Previously, at least 68 rare coding variants were reported from candidate gene sequencing studies in non-syndromic cleft lip and palate (NSCL/P), a common birth defect. Advances in sequencing technology have now resulted in thousands of sequenced exomes, providing a large resource for comparative genetic studies. We collated rare coding variants reported to contribute to NSCL/P and compared them to variants identified from control exome databases to determine if some might be rare but benign variants. Seventy-one percentage of the variants described as etiologic for NSCL/P were not present in the exome data, suggesting that many likely contribute to disease. Our results strongly support a role for rare variants previously reported in the majority of NSCL/P candidate genes but diminish support for variants in others. However, because clefting is a complex trait it is not possible to be definitive about the role of any particular variant for its risk for NSCL/P.
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, IA, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Leslie
authors.forename: J C
authors.initials: JC
authors.lastname: Murray
mesh_terms: D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D030541:Databases, Genetic; D059472:Exome; D055106:Genome-Wide Association Study; D006801:Humans; D011110:Polymorphism, Genetic