41 6 GENETICS OF SOMATIC CELLS 



disjunction during gametogenesis, either by the fertilization of an ZZ-bearing egg 

 originating through nondisjunction of the X chromosomes during meiosis, by a normal, 

 7-bearing spermatozoon, or by the fertilization of a normal, Z egg by a spermotozoon 

 containing XY due to nondisjunction during spermatogenesis. In this XXY individual, 

 cells containing the normal complement of 46 chromosomes could be expected to 

 arise by mitotic nondisjunction. Ford et al. 388 assume that such cells may exhibit a 

 selective advantage and compete successfully with their progenitors, since the loss of 

 the Y chromosome from an XXY cell would be a step in the direction of normality. 

 In fact, the work of the Harwell group on serial transplantation of bone marrow 

 through lethally irradiated mice clearly showed that different clones of cells, distinguish- 

 able by differences in their chromosomal complement, may proliferate differentially 

 even to the extent that one clone is disseminated widely and outgrows all the rest. 53 

 They also obtained evidence indicating that marrow cells deficient in chromosomal 

 segments, produced by the irradiation of normal animals, were rapidly eliminated. 



Other cases of mosaicism for the sex chromosomes, reflected in the bone marrow 

 and in other tissues, have been described by Ford 384 who found two patients with 

 Turner's syndrome, containing a mixture of XO and XX cells. These individuals 

 were assumed 384 to have originated through the union of an gamete, derived from 

 nondisjunction during meiosis, with a normal Z-bearing gamete. Mitotic nondisjunc- 

 tion of an XO cell during development would subsequently have led to normalization 

 and the appearance of an XX cell which, due to its selective advantage determined by 

 the normal chromosomal complement, would have survived well in competition with 

 its less normal progenitors. Another case of mosaicism, discovered recently by Jacobs 

 et al. 658 contained two cell classes, with 45 and 47 chromosomes, respectively, and de- 

 tailed analysis led to the conclusion that this was an XXX/XO mosaic. The pro- 

 portions of the two cell types varied quite considerably between different tissues. This 

 case was particularly interesting since it had to be attributed to nondisjunction of the 

 X chromosomes during the first cleavage division of the fertilized egg. It could not 

 have arisen during any of the later divisions, since a triple mosaic of the type XO/XX/ 

 XXX would have resulted from such an event. 



Thus aneuploidy, due to meiotic or mitotic nondisjunction, may be an important 

 factor causing mosaicism and various developmental abnormalities in higher organisms. 

 Of course, when considering isoantigenic substances such as blood groups, the restriction 

 has to be made that only variant types for which the host organism is tolerant can survive 

 and become demonstrable. This means either that they must arise during embryonic 

 life or that they must represent losses rather than changes to alternative antigenic states. 



Somatic mutation has often been postulated as an explanation of unusual findings 

 involving the ABO system to the exclusion of other blood systems. 228 No individual 

 had a history of twinning or transfusion in these cases. They include two families with 

 + A 2 mosaics, with A 2 between 8 and 12 per cent in four cases. In one woman 

 there was clear-cut partial agglutination, heterochromia iridum partialis, and the 

 A antigen was found in one small area of the decidua parietalis after the birth of a third 



