ORIGIN OF NONDISJUNCTION IN TRISOMY-8 AND TRISOMY-8 MOSAICISM

Causes of chromosomal nondisjunction is one of the remaining unanswere d questions in human genetics. In order to increase our understanding of the mechanisms underlying nondisjunction we have performed a molecu lar study on trisomy 8 and trisomy 8 mosaicism. We report the results on analyses of 26 probands (and parents) using 19 microsatellite DNA m arkers mapping along the length of chromosome 8. The 26 cases represen ted 20 live births, four spontaneous abortions, and two prenatal diagn oses (CVS). The results of the nondisjunction studies show that 20 cas es (13 maternal, 7 paternal) were probably due to mitotic (postzygotic ) duplication as reduction to homozygosity of all informative markers was observed and as no third allele was ever detected. Only two cases from spontaneous abortions were due to maternal meiotic nondisjunction . In four cases we were not able to detect the extra chromosome due to a low level of mosaicism. These results are in contrast to the common autosomal trisomies (including mosaics), where the majority of cases are due to errors in maternal meiosis.