No evidence of linkage between the transforming growth factor-alpha gene in families with apparently autosomal dominant inheritance of cleft lip and palate.
Eight families have been identified with cleft lip, with or without cleft palate (CL/P), inherited in an apparently autosomal dominant manner. Transforming growth factor-alpha (TGFA) has been tested as a candidate gene for clefting in these families. Negative lod scores were generated in an autosomal dominant model with 80% penetrance (Z = -3.152 at theta = 0.05 and Z = -2.49 at theta = 0.05 with only affected subjects scored). After testing with a reduced penetrance of 28%, less negative lod scores were generated (Z = -0.157 at theta = 0.00), but there was still no evidence of linkage. An autosomal recessive model with a penetrance of 35% was also tested. Regardless of the model used there was little evidence of linkage between TGFA and the CL/P phenotype, which is in contrast to the previously published findings of an association between TGFA and CL/P in unrelated subjects.
Molecular Genetics Unit, Institute of Child Health, London.
G M
GM
Vintiner
S E
SE
Holder
R M
RM
Winter
S
S
Malcolm
D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008957:Models, Genetic; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D016211:Transforming Growth Factor alpha / Q000235:genetics*
D016211:Transforming Growth Factor alpha