STUDIES OF THE CANDIDATE GENES TGFB2, MSX1, TGFA, AND TGFB3 IN THE ETIOLOGY OF CLEFT-LIP AND PALATE IN THE PHILIPPINES

Population-based candidate-gene studies can be an effective strategy f or identifying genes involved in the etiology of disorders where famil y-based linkage studies are compromised by lack of access to affected members, low penetrance, and/or genetic heterogeneity, We evaluated as sociation data for four candidate genes using a population from the Ph ilippines that is genetically separate from previously studied Caucasi an populations. Case ascertainment was made possible by collaboration with Operation Smile, a volunteer medical organization, which facilita ted identification of a large number of cases for study. A new allelic variant of transforming growth factor-beta3 was identified to use in these studies, After exclusion of syndromic cases of cleft lip and pal ate, no evidence for association with previously reported allelic vari ants of transforming growth factor-beta2 (TGFB2), homeobox 7 (MSX1), o r transforming growth factor-alpha (TGFA), or with the new TGFB3 varia nt was detected. Previous association studies using Caucasian populati ons of nonsyndromic cleft lip and/or palate (CL/P) and cleft palate on ly (CPO) have strongly suggested a role for TGFA in the susceptibility of clefting in humans, Exclusion of significant association in a non- Caucasian population for TGFA suggests that TGFA plays less of a role than it does in Caucasians, This may be due to multiple or different g enetic and/or environmental factors contributing to the etiology of th is most common craniofacial anomaly in the Philippine population.