Biostatistical basis of individualization and segregation analysis using the multilocus DNA probe MZ 1.3: results of a collaborative study.

A collaborative study using the multilocus minisatellite DNA probe MZ 1.3 was carried out to investigate segregation information, mutation rate, DNA fragment frequencies as well as band sharing characteristics. The fingerprint patterns of 393 children as well as 694 unrelated individuals were analysed after digestion of DNA with the restriction enzyme HinfI. A mutation rate of 1% per meiosis or 0.04% per band was found with a mean number of 26 bands/individual. It was shown that maternal and paternal fragments are inherited in equal proportions. Population frequencies of restriction fragments demonstrated a distribution with increasing frequencies in the small fragment size range below 10 kb as well as the absence of very common or very rare fragments. Our data can be used to calculate simple exclusion probabilities based on the number of non-maternal bands in the child.

Diethylnitrosamine-induced hepatocarcinogenesis in rats: a theoretical study.

Multiple data sets on hepatocarcinogenesis in rats resulting from pulse (single) or continuous exposure to diethylnitrosamine (DEN) are analyzed within the framework of a two-mutation carcinogenesis model in order to identify the underlying biological processes that control the pharmacodynamics of DEN-induced liver cancer. Our findings indicate: (1) Predictions of the two-mutation oncogenic model are consistent with empirical data on DEN-induced hepatocarcinogenesis. (2) The probability of the first genetic alteration (initiation) is linearly dependent on applied dose and decays exponentially following a pulse (single) dose or cessation of exposure. (3) The probability of initiation is proportional to the number of O4-ethyldeoxythymidine DNA adducts resulting from DEN exposure, indicating that these adducts are the likely promutagenic lesions in DEN-induced hepatocarcinogenesis. (4) The mitotic rates of initiated and transformed cells are nonlinear with dose. (5) The average growth rate of initiated hepatocytes as a function of DEN dose is related to Druckery's slope. (6) The probability of the second genetic event (transformation) is independent of applied dose, suggesting that it is the result of a spontaneous genetic alteration.

Druckery slope controlled by mitotic rate of enzymatically-altered foci.

Data on hepatocellular foci and tumors for four hepatocarcinogens are analyzed within the framework of a two-mutation model of oncogenesis to determine the biological factor(s) that control the values of N in Druckery's formula DTN = K, where T is the time to 50% tumor incidence at a daily dose D. The two-mutation oncogenic model was found to adequately reproduce the empirical data for all four hepatocarcinogens. The controlling factor of the Druckery slope N was found to be the mitotic rate (MRI) of hepatocellular foci, where MRI = CD1/N, C is a chemical-dependent constant, D is dose, and N is the Druckery slope.

[Effect of the genetic markers Kell(K1), P1, Km(1), Tf(C

This statistical analysis of the results of 288 paternity cases is a contribution to the discussion of those blood group systems to be selected for the basis of paternity expertise in the Federal Republic of Germany. When typing 22 blood-group systems in 288 one-man cases, we found exclusions in 101 (35.07%) of them. In only 83 (44.39%) of the 187 cases with nonexclusions did the resulting EM value correspond to the verbal predicate: "paternity practically proved." The results of the systems of factors Kell(K1), Tf(C,B,D), AK and 6-PGD had the smallest rate of exclusion constellations and only inferior influence on the resulting EM values. Replacing them by isoelectric focusing of the systems PGM1, Tf, Gc, Pi and PLG (plasminogen) seems to be reasonable. The factors P1 and Km(1) proved more favorable for the results of paternity cases.