title: Association of genetic variation of the transforming growth factor-alpha gene with cleft lip and palate.
abstract: Complex segregation analysis of pedigrees having nonsyndromic cleft lip with or without cleft palate (CL/P) (Chung et al. 1986; Marazita et al. 1986) has shown that a major-locus model best explains the observed recurrence of CL/P in Caucasian families. To identify this major gene, we compared the frequencies of 12 RFLPs at five loci-epidermal growth factor, transforming growth factor-alpha, epidermal growth factor receptor, glucocorticoid receptor, and estrogen receptor-in both a group of 80 subjects with nonsyndromic CL/P and 102 controls. These candidate genes were selected because studies in rodents had suggested their possible involvement in palatogenesis. A significant association was observed between two RFLPs at the transforming-growth-factor-alpha (TGFA) locus and the occurrence of clefting (P = .0047 and P = .0052). This suggests that either the TGFA gene itself or DNA sequences in an adjacent region contribute to the development of a portion of cases of CL/P in humans and provides an opportunity to begin to examine the molecular events underlying lip and palate formation.
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City 52242.
authors.forename: H H
authors.initials: HH
authors.lastname: Ardinger
authors.forename: K H
authors.initials: KH
authors.lastname: Buetow
authors.forename: G I
authors.initials: GI
authors.lastname: Bell
authors.forename: J
authors.initials: J
authors.lastname: Bardach
authors.forename: D R
authors.initials: DR
authors.lastname: VanDemark
authors.forename: J C
authors.initials: JC
authors.lastname: Murray
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D015342:DNA Probes; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007223:Infant; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D015291:Transforming Growth Factors / Q000235:genetics*
chemical_list: D015342:DNA Probes; D005819:Genetic Markers; D015291:Transforming Growth Factors