Mini Review

the origin of the extra chromosome 21 Hassold T, Sherman S. Down syndrome: genetic recombination and the origin of the extra chromosome 21. Clin Genet 2000: 57: 95–100. © Munksgaard, 2000 Despite the clinical importance of trisomy 21, we have been ignorant of the causes of meiotic nondisjunction of chromosome 21. Recently, how-ever, genetic mapping studies of trisomy 21 families have led to the identification of the first molecular correlate of human nondisjunction; i.e. altered levels and positioning of meiotic recombinational events. Specifically, increases in 0 exchange events or in distal-only or pericen-tromeric exchanges are significantly increased in trisomy 21-generating meioses. These observations have led to the idea that chromosome 21 nondisjunction requires ‘two hits’: first, the establishment in prophase I of a ‘vulnerable ’ bivalent and second, abnormal processing of the biva-lent at metaphase I or II