Oct. 27, 1923 
Otocephaly in Guinea Pigs 
167 
It may be thought that the cooperation of a large number of factors 
is necessary for the appearance of the defect and that only in the 
cluster mentioned has homozygosis been reached in a sufficient number 
of these factors to give one or two factor ratios. This hypothesis, how¬ 
ever, is untenable in view of the system of mating. Brother-sister 
mating leads automatically to rapid increase in homozygosis. After 10* 
generations less than 6 per cent heterozygosis should be left. If oto¬ 
cephaly is due to the cooperation of many factors, inbreeding should 
lead rapidly to the disappearance of otocephali in the great majority of 
lines, through homozygosis in some one or more of the normal allelo¬ 
morphs, while the few lines in which all the factors for otocephaly persist 
should be soon producing 3 :i ratios because of homozygosis in all but 
one of the factors. The history of Family 13 is wholly at variance with 
these conclusions. 
There is one mechanism by which rapid increase in homozygosis would 
be prevented. If a necessary factor for otocephaly were linked with one 
lethal factor and balanced against another, it could be carried on indefi¬ 
nitely in a heterozygous condition, otocephaly only appearing on the 
occurrence of a crossover. By complicating the situation with other 
lethals the observed results could readily be explained, including the 
sudden increases in the percentage at various points in the pedigree. 
Unfortunately other considerations make it very doubtful whether the 
assumption of balanced lethals is tenable. With balanced lethals the 
size of litter should be greatly reduced (halved except for the higher 
percentage of embryos absorbed in large litters). Family 13, as pre¬ 
viously stated, has consistently been among the best inbred families as 
regards size of litter. During the period from 1916 to 1921, in which the 
majority of its otocephali were produced, it was the best of the inbred 
families. Its average in these years has been 2.53, as compared to 2.33 in 
the total inbred stock and 2.65 in the control stock. Moreover, with 
different systems of balanced lethals among the inbred families, one 
would expect an increase in the size of litter when a female of one family 
is mated with a male of another or with a crossbred male. No such 
increase has taken place in extensive and carefully controlled experiments. 
There is indeed an important increase (about 12 per cent) when the cross¬ 
bred daughters of such matings are themselves mated, whether with a 
brother, an unrelated inbred, or a crossbred. But this indicates that size 
of litter is determined by the breeding of the dam, and not of the young 
themselves, as should be the case with balanced lethals. 
If the otocephali are not Mendelian segregates the possibility must be 
considered that they are mutations or due to chromosome aberrations of 
some sort. The sporadic occurrence outside of Family 13 is reasonably 
in harmony with this view. The number and distribution in Family 13, 
however, can not be explained satisfactorily in this way. It seems clear 
that a genetic factor or factors for otocephaly must be transmitted by 
normals in Family 13. 
Thus neither Mendelian segregation, even with balanced lethals, nor 
mutation, is a satisfactory explanation by itself of the observed distribu¬ 
tion. Under both these explanations it is assumed that the otocephali 
as a group differ genetically from all normals. But even if the difficulties 
with these purely genetic explanations were less, the continuous grada¬ 
tion from a condition which can not certainly be distinguished from 
normal (grade 1) to the almost completely headless condition of grades 
11 and 12, should lead us to suspect that some guinea pigs, at least, with 
