title: Exclusion of candidate genes from a role in cleft lip with or without cleft palate: linkage and association studies.
abstract: Candidate genes and marker loci for cleft lip/palate (CL/P) were tested using linkage analyses and association studies. Eight British families with apparent autosomal dominant inheritance of non-syndromic CL/P participated in the linkage analyses while the association analyses involved 61 unrelated British white people with CL/P and 60 controls. The report of an association between RARA (17q21) and unrelated Australian persons with CL/P (p = 0.016) was not confirmed in British CL/P persons (chi 2 = 0.954, p > 0.1). There was also no evidence of linkage between RARA and the eight CL/P families (Z = -3.211, theta = 0.001). Linkage was excluded between familial CL/P and F13A1 (map position 6p24-25) with an observed maximum lod score of Z = -2.052 at theta = 0.05. No association was found between alleles at VIM (10p13) and the British CL/P subjects (chi 2 = 0.110, p > 0.5). Multipoint analysis excluded linkage between familial CL/P and the markers D1S65 and D1S58 which flank the Van der Woude syndrome locus with a maximum lod score of Z = -4.0. This suggests that the genetic defect underlying VWS is not the same as in non-syndromic CL/P. There was no evidence of linkage between CRTL1 (5q15) and the eight CL/P families (Z = -3.466, theta = 0.05).
authors.affiliation: Molecular Genetics Unit, Institute of Child Health, London, UK.
authors.forename: G M
authors.initials: GM
authors.lastname: Vintiner
authors.forename: K K
authors.initials: KK
authors.lastname: Lo
authors.forename: S E
authors.initials: SE
authors.lastname: Holder
authors.forename: R M
authors.initials: RM
authors.lastname: Winter
authors.forename: S
authors.initials: S
authors.lastname: Malcolm
mesh_terms: D001483:Base Sequence; D016009:Chi-Square Distribution; D002879:Chromosomes, Human, Pair 10; D002895:Chromosomes, Human, Pair 5; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D017931:DNA Primers; D004276:DNA, Satellite / Q000235:genetics; D016326:Extracellular Matrix Proteins; D005787:Gene Frequency; D008040:Genetic Linkage; D006801:Humans; D008126:Lod Score; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics; D011509:Proteoglycans / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics; D000072482:Retinoic Acid Receptor alpha; D014746:Vimentin / Q000235:genetics; D000099249:Proteoglycan Link Protein
chemical_list: D017931:DNA Primers; D004276:DNA, Satellite; D016326:Extracellular Matrix Proteins; D011506:Proteins; D011509:Proteoglycans; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014746:Vimentin; D000099249:Proteoglycan Link Protein; C000607071:RARA protein, human