The goal of this section is to determine the influence of genetic factors upon the expression of early onset periodontal diseases and upon related etiologic and pathogenic factors. Preliminary analyses of 33 families of probands with juvenile periodontitis (JP) or severe periodontitis (SP) give strong evidence for a genetic component in the expression of JP that is probably autosomal recessive. In order to directly use complex segregation analysis rather than merely comparing the magnitudes of the likelihoods of competing genetic hypotheses, continued active recruitment of family members of the 199 probands (in 198 families) that we have identified will be undertaken. In addition, we proposed to search for a genetic linkage between JP-SP ad a known chromosomal marker to confirm genetic segregation and to map jp to the chromosomal location of the marker. For initial studies, in 5-10 multigenerational JP or SP families, DNA restriction fragment length polymorphism (RFLP) status will be determined and probes will be used for the X- chromosome (to rule out X-linked transmission) and for chromosome 4q. Other probes encompassing as much of the genome as feasible will be then used if necessary. In related studies, specific heterogeneity hypotheses will be tested to determine if there is heterogeneity in the etiology of early on set periodontitis. Characteristics such as sex of proband, occurrence of JP only vs. JP and SP in a family, high vs, low antibody titers to certain bacteria in families, and Caucasian vs. Black families will be used to subdivide the data for segregation analyses. In addition, genetic analysis of patterns of the antibody response to plaque organisms and PMN chemotaxis responses (using existing data collected over the past 5 years) will be attempted.
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