A genomic analysis to comprehend the genetic mechanisms of cleft lip and palate in Brazilian population

Abstract

Nonsyndromic cleft lip with or without cleft palate (NS CL/P) is a complex disease that represents the most common craniofacial defect at birth. A genetic role in the etiology of NS CL/P is strongly suggested, but the only susceptibility loci widely corroborated (the IRF6 gene and a gene desert at 8q24 region) increase low risk to the disease. Considering the recent failures of linkage and association studies in identifying the variants which explain the high heritability of NS CL/P, and assuming the existence of rare high-effect variants which might have been undetected by the current approaches, we are proposing the exome sequencing of at least 9 individuals of 3 families, in which NS CL/P is recurrent. The identified variants will be validated by Sanger sequencing and tested in a case-control study with a major sample. (AU)