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 results for the chromosome 6q region and reveal a novel candidate gene for CL±P.
Alexandre R
AR
Vieira
Flavia M
FM
de Carvalho
Lindsay
L
Johnson
Lauren
L
DeVos
Alexa L
AL
Swailes
Megan L
ML
Weber
Kathleen
K
Deeley
D000483:Alleles; D002874:Chromosome Mapping; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D010375:Pedigree; D010679:Philippines; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*
D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C437717:TULP4 protein, human
EPB41L2; SAMD3; TMEM200A; linkage; tubby domain superfamily protein; tubby like protein 4