Dentinogenesis imperfecta is a dominantly transmitted disease affecting between 1 in 6000 to 1 in 8000 children. It results from an unknown error in the mesodermal development and affects only the formation of dentin in teeth. Its phenotype includes opalescent teeth having a blue-gray or amber brown color. Crowns, roots, pulp chambers, and root canals can also demonstrate characteristic abnormalities. The gene controlling the expression of this disease has been mapped to a chromosomal locus approximately 5 to 9 centiMorgans (about 5 to 9 million nucleotide bases) from the chromosomal locus of the Group-Specific Component (Gc). The Gc plasma protein transports vitamin D and its metabolites. Although this protein exists as three genetic types in all populations studied, little is known about its function or conformation. The recent cloning of the cDNA encoding Gc will provide the deduced amino sequence of this molecule and its leader sequence. The proposal described here is to utilize the cDNA probe encoding Gc to map Gc to a more precise location on the long arm of chromosome 4, to detect DNA polymorphisms (RFLPs) that occur in this chromosomal region, and to use the RFLPs detected by the Gc probe to map the gene that expresses dentinogenesis imperfecta to a precise subregion on human chromosome 4. This will be carried out by multipoint linkage analysis. Radiolabeled probes detecting polymorphisms occurring on chromosome 4 will be used for Southern hybridization analysis on filters containing endonuclease digests of genomic DNA obtained from lymphocytes of members of families in which dentinogenesis imperfecta is segregating. The long term goal of this work will be to clone and characterize the defective gene leading to dentinogenesis imperfecta. Exploitation of recombinant DNA techniques offers a promising means of detecting a genetic marker that will be available for tracking the dentinogenesis imperfecta gene in affected families.
Yang, F; Naylor, S L; Lum, J B et al. (1986) Characterization, mapping, and expression of the human ceruloplasmin gene. Proc Natl Acad Sci U S A 83:3257-61 |