The objectives of this project are (1) to detect natural and induced mutations in mice, (2) to achieve understanding of the molecular events occurring in the process of mutation induction, and (3) to relate these events to the life, form and function of the mammalian organism, including man. Our project is relevant to the problem of human exposures to environmental chemicals, including mutagens and carcinogens, and to the increased risk of genetic disease that the offspring of exposed individuals may incur. We have detected many mutations at specific biochemical loci with electrophoretic methods, characterized several normal and mutant genes (and gene products), and examined the offspring of mutagen-treated and control parents for a physical manifestation of polygenic mutations affecting the skeleton. Recently, we developed an expanded set of skeletal characters and an independent method for evaluating metrical variation using X, Y coordinate data obtained using enlarged bone images projected on a digiting tablet. Applying these newly acquired means, we recently completed analysis of 1030 progeny from treated and control DBA/2J x C57BL/6J parents and discovered one group with a very highly statistically significant increase in variability. Much of this variation is too slight to be noticed by ordinary visual inspection, but a large proportion of animals were affected in the one group. These results suggest that morphometrical analysis may provide a more powerful tool to investigate problems of genetic risk than was previously believed. The results also suggest that these methods may be much more efficient and relevant than any available specific-locus test.
