PROBLEMS OF MEASUREMENT OF MUTATION RATES 15 



this figure, you get a completely different result on extrapolating 

 back. The result is that you have 30 years' worth of mutants present 

 at birth. 



Glass: What is the figure, 1.26? 



Atwood: That is the factor by which the apparent rate in fathers 

 over 35 differs from the apparent rate in those under 30. 



Lederberg: Is one permitted to say that there is a significant 

 difference in the age dependence of these three conditions? 



Atwood: No, I don't think so. 



Lederberg: Then there is really not much point in trying to set the 

 models against any one of these alternatives, since they give con- 

 trary results, and you can't be sure that the results are different from 

 one another. 



Atwood: The data for these three were pooled for the purpose of 

 comparison with achondroplasia. To wind up the question of age 

 dependence, I would say that if, with accumulation of further data, it 

 looks as though there is no significant age dependence, then that sug- 

 gests that the mutations occur mainly during the prereproductive 

 period, and the stem line mutation rate is too low to measure. On the 

 other hand, if the data are good enough to get the slope of age de- 

 pendence, then the relative contributions of the clonal and stem line 

 periods can both be estimated. 



Lederberg: Can one lump those data? Since they are not hetero- 

 geneous, they are homogeneous. You could add them together and 

 arrive at the conclusion that there is an age dependence in mutation 

 rate, implying that mutations are taking place. 



Atwood: Some age dependence must exist, unless you are willing to 

 believe that the cell mutation rate during the reproductive period 

 is immeasurably small. 



Neel: I think that we can conclude that there is an age dependence 

 effect, but the achondroplasia situation stands out as somewhat differ- 

 ent from the other situations in magnitude (25, 29). 



Atwood: Yes, it is very different. It is sort of a male counterpart of 

 the situation with mongolism, where we know that the cause is not a 

 mutation of the kind we want to talk about. 



Novick: Kim, isn't it the frequency you're speaking about, not the 

 mutation rate? You used the expression that there is a 3.8 times higher 

 mutation rate for the older group than the younger. 



Atwood: I meant the relative frequency of mutant gametes. We 

 should understand, though, that this is synonymous with mutation 

 rate as ordinarily expressed in man. 



