Genetic linkage of the dentinogenesis imperfecta type III locus to chromosome 4q.
Dentinogenesis imperfecta type III (DGI-III) is an autosomal-dominant disorder of dentin formation which appears in a tri-racial southern Maryland population known as the "Brandywine isolate". This disease has suggestive evidence of linkage to the long arm of human chromosome 4 (LOD score of 2.0) in a family presenting with both juvenile periodontitis and DGI-III. The purpose of this study was to screen a family presenting with only DGI-III to determine if this locus was indeed on chromosome 4q. Furthermore, we wanted to determine if DGI-III co-localized with dentinogenesis imperfecta type II (DGI-II), which has been localized to 4q21-q23. Therefore, a large kindred from the Brandywine isolate was identified, oral examination performed, and blood samples collected from 21 family members. DNA from this family was genotyped with 6 highly polymorphic markers that span the DGI-II critical region of chromosome 4q. Analysis of the data yielded a maximum two-point LOD score of 4.87 with a marker for the dentin matrix protein 1 (DMP1) locus, a gene contained in the critical region for DGI-II. Our results demonstrated that the DGI-III locus is on human chromosome 4q21 within a 6.6 cM region that overlaps the DGI-II critical region. These results are consistent with the hypothesis that DGI-II is either an allelic variant of DGI-III or the result of mutations in two tightly linked genes.
MacDougall
M
M
Department of Pediatric Dentistry, University of Texas Health Science Center at San Antonio, 78284-7888, USA.
Jeffords
L G
LG
Gu
T T
TT
Knight
C B
CB
Frei
G
G
Reus
B E
BE
Otterud
B
B
Leppert
M
M
Leach
R J
RJ
D010520:Aggressive Periodontitis / Q000235:genetics; D000483:Alleles; D002874:Chromosome Mapping / Q000379:methods*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D003811:Dentinogenesis Imperfecta / Q000145:classification / Q000235:genetics*; D016326:Extracellular Matrix Proteins; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D008396:Maryland; D009154:Mutation / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics
C513309:DMP1 protein, human; D016326:Extracellular Matrix Proteins; D005819:Genetic Markers; D010750:Phosphoproteins; D004247:DNA