A THEOREM ON THE GENETICS OF SOME CONGENITAL MALFORMATIONS
From a consideration of the empirical risks of repetition of cleft lip, cleft palate, and pyloric stenosis within a family, a general theorem was devised in which genetic moiety, neomutational portion, dominance, and penetrance were interrelated. This theorem made possible the calculation of estimates for these parameters and offered an explanation for certain paradoxes in the distribution of the cases in the family. It was likely that such conditions do have a partial genetic etiology, with reduced penetrance, and that dominance varies from trait to trait. A portion of the occurrence of these congenital anomalies can be ascribed to mutations arising in each generation. An example is cited of a mutagenic influence that might increase the incidence of malformations, namely, the exposure of human populations to ionizing radiation, and a quantitative estimate of the latter risk was proposed. That the fraction (m) of congenital anomalies due to radiation appears small for two of the traits discussed is not surprising, inasmuch as these conditions are compatible with survival and retention of a good part of reproductive fitness. Accordingly, higher values of m should be expected for the more severe anomalies that are lethal or entail a near-complete loss of reproductive fitness. Unpublished results on major congenital anomalies in large populations gives evidence saggesting a minimum mean value m = 0.35 for the ensemble of such cases. The importance of the parameter in lies in the prediction of the effect of a given mutagenic influence upon the incidence of developmental effects. This can be expressed by i = (D/ sub m/)/(D/sub 2/), where i is the increase in incidence in the offspring of the parental generation (P/sub 1/) to which is applied a dose D of an influence for which the mutation-doubling dose is D/sub 2/. In the case of the diagnostic use of x-rays in North America at this time (estimated at 4.5-r gonad dose per 30 yr, i.e. per generation) substitution in the equation of the value m = 0.35 leads to an estimate: i = (4.5 x 3.5)/30 = 0.05, i.e., a 5% increase in the incidence of congenital malformation in the first filial generation, D/sub 2/ for x rays being provisionally estimated at 30 r. The role of the portion (g) of genetically transmitted anomalies must also be considered since the genetic moiety is all mutational in origin: some of it (m) arising in the present parental generation, the remainder (g/sub 1/) having arisen in an indefinite number of generations prior to the P/sub 1/. While an increase in m is expected in the first filial generation (F/sub 1/) from a dose D/sub 2/ applied to the P/sub 1/, a total increase in g will result, spread over the entire posterity. If D/sub 2/ is applied to all succeeding generations (permanent doubling), the expected increase per generation rises from m to reach g at equilibrium (after many generations). The question of the induction of mutations by radiation is a vital one, and contrary to the negative impression favored by some official spokesmen, it has been shown that paternal irradiation by the atomic bombs in Japan was followed by a statistically significant increase of reproductive wastage in the offspring and that the magnitude of the increase in major congenital malformations was quite near that expected in the F/sub 1/ from the estimated amount of radiation received. This was of the order of a 1% increase per roentgen gonad dose. (BBB)
- Research Organization:
- Univ. Ottawa
- NSA Number:
- NSA-18-003506
- OSTI ID:
- 4128915
- Journal Information:
- Acta Genet. Statist. Med., Vol. Vol: 12; Other Information: Orig. Receipt Date: 31-DEC-64
- Country of Publication:
- Country unknown/Code not available
- Language:
- English
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