Evidence Suggesting a Multigenic Origin of Membranous Septal Defect in Rats
The study was designed to assess the relative importance of parity, parental age and the fetal genome in the etiology of congenital interventricular septal defects in a subline of Long-Evans rats with a high incidence of malformation (25%). Analysis of successive litters produced in 27 full sibships indicated that parity and parental aging had no consistently significant influence on the incidence of defects. Relatively consistent litter incidences within sibships but highly significant differences in the mean litter incidences of the different sibships support the hypothesis that the fetal genome is of primary etiologic importance. Analysis of the half-sibships produced by 12 males in sequential matings with different young virgin females indicated that neither paternal age nor a parental age differential significantly influenced the incidence of defects. Highly significant differences between the half-sibships in respect to mean litter incidences of malformation were attributable to highly significant differences between sires, significant differences between dams and considerable within litter variation. Analysis of the parental-offspring distribution of defects rules out the possibility of fully penetrant unifactorial inheritance but suggests that ventricular anomalies are transmitted in accordance with a polygenic, quasi-continuous inheritance pattern.
- half-sibship analysis
- genetic transmission
- parental offspring correlation
- familial clustering
- polygenic, quasi-continuous inheritance
- parental aging
- sire influence
- Received January 6, 1969.
- Accepted March 10, 1969.
- © 1969 American Heart Association, Inc.