Variation in alphoid DNA size and trisomy 21: a possible cause of nondisjunction

The cause of nondisjunction of chromosome 21 remains largely unknown. In th e present report, we investigate the hypothesis that variation in alphoid D NA size has a role in trisomy formation. Pulsed-field gel electrophoresis w as used to examine the chromosome 21 alphoid DNA array lengths in 23 famili es tall of Northern European ancestry) with an affected child with trisomy 21 in whom the parental and meiotic origin of nondisjunction had been deter mined as maternal meiosis I, and in 38 controls. Initially, the combined al phoid size of both chromosome 21 homologues was assessed. This indicated an association between small combined alphoid size and maternal meiosis I non disjunction. Moreover, in a subset of the families under study (n=12), it w as possible to study the alpha 21-I size of individual chromosome 21 homolo gues (simple alphoid size); this provided further evidence that the risk fo r nondisjunction is related to the size of the alphoid array of one of the two chromosome 21 homologues being small.