title: Further evidence suggesting a role for variation in ARHGAP29 variants in nonsyndromic cleft lip/palate.
abstract: BACKGROUND
  Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect of complex etiology. Several genes have been implicated in the etiology of NSCL/P, although only a few have been replicated across datasets.
  
  
  METHODS
  ARHGAP29 was suggested as a candidate gene for NSCL/P as it is located in close proximity to ABCA4 (1p22), a gene previously identified in a genome-wide association study of NSCL/P.
  
  
  RESULTS
  Rare, potentially damaging, coding variants in ARHGAP29 were found in NSCL/P cases, and its expression was detected during murine craniofacial development. In this study, we investigated whether variations in ARHGAP29 were associated with NSCL/P in our family based dataset. Five single-nucleotide polymorphisms (SNPs) flanking and within ARHGAP29 were genotyped in our NSCL/P datasets consisting of simplex and multiplex families of non-Hispanic white (NHW, primarily European) and Hispanic ethnicities. Results showed strong association of three ARHGAP29 SNPs with NSCL/P in the NHW families. Two intronic SNPs (rs1541098 and rs3789688) showed strong association with NSCL/P in all NHW families (p = 0.0005 and p = 0.0002, respectively), and simplex NHW families (p = 0.003 for both SNPs). A SNP in the 3' untranslated region (rs1576593) also showed strong association with NSCL/P in all NHW families (p = 0.002), and the multiplex subset (p = 0.002). ARHGAP29 SNP haplotypes were also associated with NSCL/P. Evidence of gene-gene interaction was found between ARHGAP29 and additional cleft susceptibility genes.
  
  
  CONCLUSIONS
  This study further supports ARHGAP29 as a candidate gene for human NSCL/P in families of Caucasian descent.
authors.affiliation: Department of Endodontics, University of Texas Health Science Center at Houston School of Dentistry, Houston, Texas; Craniofacial Research Center, University of Texas Health Science Center at Houston School of Dentistry, Houston, Texas.
authors.forename: Ariadne
authors.initials: A
authors.lastname: Letra
authors.forename: Lorena
authors.initials: L
authors.lastname: Maili
authors.forename: John B
authors.initials: JB
authors.lastname: Mulliken
authors.forename: Edward
authors.initials: E
authors.lastname: Buchanan
authors.forename: Susan H
authors.initials: SH
authors.lastname: Blanton
authors.forename: Jacqueline T
authors.initials: JT
authors.lastname: Hecht
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002971:Cleft Lip / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D002972:Cleft Palate / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D004843:Epistasis, Genetic; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007438:Introns; D008297:Male; D017058:Mexican Americans; D051379:Mice; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D044465:White People
chemical_list: D020413:3' Untranslated Regions; C500429:ARHGAP29 protein, human; D020690:GTPase-Activating Proteins
keywords: ARHGAP29; association; cleft lip/palate; gene; gene interaction; haplotype