MAMMALIAN RADIATION GENETICS 139 



The linked-lethal method can be increased in its efficiency through the use of a 

 number of independent marker genes. 517 The statistical complications of the method 

 have been worked out by Haldane. These include the question of allowance for chance 

 fluctuations in the F 2 segregation ratio and the length of the chromosome scanned on 

 either side of the marker gene. The total swept length will naturally increase with the 

 number of markers employed and with the number of F 2 progeny raised. 



The method requires three generations; the first is from crossing the homozygous 

 marker stock inter se, one parent of which has been irradiated. The second generation 

 is an outcross of the marker stock which may now carry a lethal in the heterozygous 

 form to a wild strain. The use of what might appear to be an extra generation of 

 breeding, that is, the carrying of the homozygous marker stock one generation beyond 

 the irradiated generation, eliminates sibmating the progeny of the irradiated parents 

 and the accompanying chance of introducing a lethal from both parents independently 

 induced. In other words, the second generation progeny trace back to only a single 

 irradiated gamete in the original parents. The third generation is produced by 

 sibmating the second generation progeny and significant deviations from the expected 

 3 : 1 ratios are sought. 



Carter 158 tested the system of Haldane with a stock carrying seven recessive, 

 visible genes. These are the same as those noted earlier with the exception that 

 pink-eye (p) had been replaced by waved-l (wa-\). The results suggested that the dose 

 required to induce one autosomal recessive lethal per gamete in spermatogonia is 

 probably no less than about 800 r of X rays delivered as a single dose. Carter con- 

 cluded that the method is far less efficient than the specific-locus method for the detection 

 of lethal mutations. 



An elaboration of the linked lethal procedure has also been described by Carter. 170 

 This involves the use of linked marker genes and the detection of lethals located be- 

 tween the markers. On a theoretical basis, Carter could not conclude that it would be 

 more efficient than the procedure employing independent markers. Apparently, the 

 method has not been subject to experimental test. Haldane, in an appendix to Carter's 

 paper, noted that the use of linked markers could be reasonably efficient as a means of 

 detecting sublethal recessive mutants, at least for sublethals with a viability between 

 about 5 and 50 per cent. Further exploration of these techniques in the laboratory 

 would appear desirable. 



Still another procedure available for the detection of recessive lethals has been 

 described and tested by Carter. 165 This test uses the reduction in litter size produced 

 by the sons of irradiated mice, when these sons are crossed to their daughters. Thus, 

 this is an application of the backcross procedure previously described that can also be 

 used for detection of visible mutations. The probability of homozygous expression of 

 a recessive lethal in the backcross progeny is again one in eight, which now is detected 

 as a one-eighth reduction in litter size in comparison to the control. The regression of 

 litter size on radiation dose was employed for the analysis and led to the conclusion 

 that a dose of about 300 r produced one recessive lethal per gamete in postmeiotic male 



