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

Abstract

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.

Keywords

EPB41L2 SAMD3 TMEM200A

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