INTERFERON ACTION AND CHROMOSOME-21 TRISOMY (DOWN-SYNDROME) - 15 YEARS LATER

A hypothesis relating interferon action and the chromosome 21 trisomy genotype and phenotype was presented in this journal in 1980. Since th at time a number of additional genes involved in interferon action hav e been mapped to the distal Down Syndrome region of chromosome 21 and a growing literature has documented highly relevant pleiotropic effect s of interferon in the brain. Thus, interferon continues to provide a potential basis for the phenotypic anomalies seen in the interferon su persensitive Down Syndrome patient. Further, the hypothesis that ribos omal RNA gene ''satellite association'' induced by interferon action i s involved in the induction of chromosome 21 misdistribution at meiosi s, is supported by extension of the cyclic correlation of Down Syndrom e prevalence and virus epidemics, first observed by Stoller & Collmann in Australia from 1942 to 1964, to incidence data gathered by the CDC in the U.S. from 1968 to 1992. In addition, data from spontaneous abo rtuses and gametes assembled from the literature argue for a uniquely high frequency of chromosome 21 hyperploidy which suggests that the ge nes present on chromosome 21 play a role in its frequent misdistributi on at meiosis. Taken together, these observations provide continued su pport for the hypothesis presented in 1980 that interferon action coul d be involved in the induction of both the trisomy 21 genotype and its resultant phenotype. (C) 1996 Academic Press Limited