Results of epidemiological and genetic studies indicate that there is a genetic component for the etiology of certain forms of early onset periodontitis (EOP) such as juvenile periodontitis. Segregation analyses of families with EOP suggest a gene(s) of major effect plays a role in the etiology of several forms of EOP. However, investigations of this genetic predisposition have been hampered by problems of inaccurate disease diagnosis and disease heterogeneity, thus stifling a promising avenue of research into the etiology of EOP. Severe early onset periodontal disease is also known to occur in Papillon Lefevre Syndrome (PLS). We have identified a very large extended kindred with many individuals affected by PLS. The problems inherent in previous genetic studies of EOP are not present in this kindred, providing a unique, naturally occurring human model for the genetic analysis of early onset periodontitis in PLS. The periodontal research group at Hadassah, (Israel) has been studying this extended kindred for more than 10 years. These family members have been examined clinically, and diagnosed for the PLS. We propose to capitalize on this unique resource by conducting molecular genetic studies with the goal of identifying the specific gene(s) and the biochemical and physiological processes that underlie risk for severe periodontal destruction in PLS.
Our specific aims are to apply genetic linkage and association techniques to PLS affected families using DNA polymorphism's genotyped by RFLP and PCR methods for selected candidate loci such as Keratin types I and II, HLA class II antigens, chemotactic associated protein GP110, and DGK, a major transduction enzyme in PMNs. Thirty cc peripheral blood will be obtained from each family member and high molecular weight DNA will be prepared by isolation of nuclear pellets by standard techniques. Linkage studies will be performed by cleaving genomic DNA with restriction endonucleases, and determining restriction fragment length polymorphism status of individuals with specific probes from the region of candidate genes. The lod score method will be used to calculate the likelihood of linkage of PLS with the candidate chromosomal markers. Mapping PLS to the chromosomal location of a candidate DNA marker will verify the role of the candidate gene in the disease process and enable further study of the actual mechanism of periodontal destruction in PLS.
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| Hart, T C; Champagne, C; Zhou, J et al. (1994) Assignment of the gene for diacylglycerol kinase (DAGK) to human chromosome 12. Mamm Genome 5:123-4 |
