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Nonsyndromic cleft lip/palate (NSCLP) is a congenital malformation with features of a complex genetic trait. Several studies have reported positive association and linkage between NSCLP and microsatellite markers in the 4q28-4q33 region particularly with the D4S192 (4q31) marker. We hypothesized that the candidate genes SMAD1 and HHIP (4q31) could be involved in the etiology of NSCLP based on previous positive linkage results and their important role in maxillofacial development. We evaluated the possible association between microsatellite markers located at less than 1 cM from these genes and NSCLP using a sample of 58 Chilean case-parent trios. Microsatellite markers were analyzed using the polymerase chain reaction (PCR) with fluorescent labeled primers. Electrophoresis of the PCR products was performed on a laser-fluorescent automatic DNA sequencer. The extended transmission disequilibrium test (ETDT) was used to analyze allelic transmissions from the parents to their affected progeny. No significant association due to linkage disequilibrium was detected between both markers and NSCLP

Assessment of the association between SMAD1 and HHIP gene variation and non-syndromic cleft-lip palate in Chilean case-parent trios