title: Candidate genes for oral-facial clefts in Guatemalan families.
abstract: Nonsyndromic cleft lip +/- cleft palate (CL/P) is a complex trait of unknown etiology. Most genetic studies of CL/P define affection status in a way that ignores subtle subclinical manifestations, resulting in a potential loss of statistical power. This study investigated 10 candidate genes in 155 individuals from 25 Guatemalan CL/P families. High-resolution ultrasound images of the orbicularis oris (OO) muscle were obtained. CL/P was present in 28 family members; an additional 10 had subcutaneous OO muscle defects. Family-based association studies were performed for both narrow (CL/P only) and broad (CL/P plus OO muscle defects) definitions of affection status. PVRL1 was significantly associated under both definitions (P = 0.04, narrow; P = 0.02, broad). Association with JAG2 improved from P = 0.09 under the narrow definition to P = 0.04 under the broad definition. Broadening the oral-facial cleft phenotype to include subclinical variants may improve power in genetic studies.
authors.affiliation: Center for Craniofacial and Dental Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA. neiswank@sdmgenetics.pitt.edu
authors.forename: Katherine
authors.initials: K
authors.lastname: Neiswanger
authors.forename: Frederic W B
authors.initials: FW
authors.lastname: Deleyiannis
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Avila
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Cooper
authors.forename: Carla A
authors.initials: CA
authors.lastname: Brandon
authors.forename: Alexandre R
authors.initials: AR
authors.lastname: Vieira
authors.forename: Negin
authors.initials: N
authors.lastname: Noorchashm
authors.forename: Seth M
authors.initials: SM
authors.lastname: Weinberg
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Bardi
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Murray
authors.forename: Mary L
authors.initials: ML
authors.lastname: Marazita
mesh_terms: D002869:Chromosome Aberrations; D002971:Cleft Lip / Q000208:ethnology* / Q000235:genetics* / Q000601:surgery; D002972:Cleft Palate / Q000208:ethnology* / Q000235:genetics* / Q000601:surgery; D006166:Guatemala; D006801:Humans; D011960:Receptors, Estrogen / Q000235:genetics*; D000094524:Gasdermins
chemical_list: D011960:Receptors, Estrogen; C111432:GSDME protein, human; D000094524:Gasdermins