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

• Published in: The Cleft palate-craniofacial journal 2015-03, Vol.52 (2), p.128-134
• Main Authors: Vieira, Alexandre R., De Carvalho, Flavia M., Johnson, Lindsay, DeVos, Lauren, Swailes, Alexa L., Weber, Megan L., Deeley, Kathleen
• Format: Article
• Language: English
• Subjects: Alleles; Chromosome Mapping; Chromosomes; Cleft Lip - genetics; Cleft Palate - genetics; Dentistry; Female; Genes; Genetic Linkage; Genetic Predisposition to Disease; Genome, Human; Genomes; Genomics; Genotype; Humans; Male; Pedigree; Philippines; Polymorphism, Single Nucleotide; Proteins; Proteins - genetics; Software; Studies; Teeth
• ISSN: 1055-6656; 1545-1569
• DOI: 10.1597/13-023

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 results for the chromosome 6q region and reveal a novel candidate gene for CL±P.