MAMMALIAN RADIATION GENETICS 137 



The specific-locus test procedure is a standard genetic test system that has been 

 employed in Drosophila genetics for many years. A wild-type mouse is irradiated and 

 mated to an animal from a multiple recessive tester stock. The immediate progeny 

 are then screened for the appearance of a mutation at any of the loci marked in the 

 parent from the tester stock. Since these F a mice are all heterozygous for the markers, 

 a new mutation at any of the loci should appear in this first generation. Mutants 

 with intermediate degrees of expression can also be detected with some degree of 

 precision. Subsequent tests, of course, can check for such homozygous effects as 

 reduced fertility, lethality, reductions in growth rate, and so forth. 



The specific-locus procedure is limited by the number of mutants that can be 

 carried in one stock without seriously reducing viability and reproductive performance. 

 Another problem is that of overlapping phenotypes ; the array of mutants must be 

 discrete and separable in their expression. The test stock used in both U.S. and 

 British genetics programs using mice at the Oak Ridge National Laboratory (Dr. W. L. 

 Russell and colleagues) and the Atomic Energy Research Establishment, Harwell, 

 England (Dr. A. G. Searle and colleagues, previously Dr. T. C. Carter), respectively, 

 is the seven-locus stock containing the recessive genes: a (nonagouti), b {brown), c ch 

 {chinchilla), d {dilute), p {pink-eye), s {piebald), and se {short-ear). This stock was 

 synthesized by Dr. W. L. Russell at Oak Ridge specifically for studies of mutation 

 rate. 1134 



The bulk of information on mutation rates in mammals has been developed from 

 this tester stock, an obvious limitation to current knowledge. It can only be assumed 

 that these seven loci are fully representative of mutability and viability of all genes. A 

 certain degree of doubt is raised by the fact that there is a greater than thirtyfold 

 difference in the spermatogonial mutation rates for several of the loci. 1138 



Alternative methods for detecting the mutation rate for recessive visible genes 

 require three generations of breeding rather than only one for the above procedure. 

 These methods screen the whole genome and require the segregation of the new 

 mutant in homozygous form in the third generation. One method, the backcross 

 method, involves the outcrossing of a son of an irradiated parent and then backcrossing 

 one of his daughters to himself. If the first-generation son carried a mutant, there 

 would be a probability of 0.5 for its transmission to the second-generation daughter. 

 If she carried the mutant, then the third-generation, backcross progeny would have a 

 one-in-four chance of segregating the new mutant in homozygous form. Altogether, 

 the chance of segregation in the third generation is only one in eight, which is not 

 very efficient. The method was employed in the early work of Hertwig 549 and also 

 by Carter and Phillips. 178 The second method for screening the entire genome 

 requires three generations of full-sibling matings. This procedure is only half as 

 efficient as the backcross method and has been used, apparently only briefly, by Carter 

 and Phillips. 175 



Aside from the inherent disadvantages of these two methods of gametic analysis 

 with respect to experimental economy, they will not succeed in detecting mutations 



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