Fine Mapping of 6q23.1 Identifies TULP4 as Contributing to Clefts.

Objective: The aim of this work was to fine-map the region 6q23.1, which obtained suggestive linkage signal (logarithm of the odds [LOD] score = 2.22 under a recessive model) to cleft lip with or without cleft palate (CL±P) in our previous genome-wide linkage scan to identify possible genetic variants that may contribute to CL±P. Design: We used densely spaced markers spanning the entire 6q23.1 region to test for association with CL±P in a family cohort sample. Setting: Clinical information and DNA samples were obtained from families in the Philippines at their homes or primary health care clinics. Participants: The study sample consisted of 477 subjects (224 females and 253 males), segregating isolated CL±P, from 72 living in the same area in the Philippines. Main Outcome Measure: Overtransmission of alleles to persons born with CL±P. Results: We found statistical evidence of association between a marker of TULP4 (rs651333) with CL±P (P = .00007). Conclusions: Our results further support the linkage resu...