Nonsyndromic cleft lip with or without cleft palate (NSCL±P) is the most common orofacial birth defect, exhibiting variable prevalence around the world, often attributed to ethnic and environmental differences. Recent genome-wide association studies (GWAS) have identified several genomic susceptibility regions for NSCL±P, mostly in European-derived or Asian populations. The genetic predisposition to NSCL±P is ethnicity-dependent, and the genetic basis of susceptibility to NSCL±P likely varies among populations. The Brazilian population is highly admixed, with highly variable ancestry; thus, the genetic determinants of NSCL±P susceptibility may be quite different. The aim of this study is tested association of single-nucleotide polymorphisms (SNPs), previously identified by GWAS in other populations, with NSCL±P the Brazilian population. Samples from 5 Brazilian states (BA, MG, PA, PB and PR) will be utilized and the influence of the genomic ancestry will be corrected by the characterization of 40 biallelic short insertion/deletion polymorphic markers (INDELs). The SNPs rs7552 in 2p24.2, rs8049367 in 16p13.3, rs1588366 in 17q23.2 and rs73039426 in 19q13.11 will be genotyped using TaqMan 52-exonuclease allelic discrimination assays in 300 trios (two living biological parents and one child affected with NSCL±P) and in another set of samples containing 250 samples of NSCL±P and 600 unaffected controls for a case-control approach. The results will be subjected to association tests including allelic (aTDT) and genotypic (gTDT) transmission disequilibrium test and case-control structured analysis in which the genetic ancestry variation of each individual is taken into account. This study may contribute for the understanding of the etiologic factors related to NSCL±P pathogenesis, as well as reveal the environment and genetics factors of risk for NSCL±P in the Brazilian population.
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