CENTROMERIC INACTIVATION IN A DICENTRIC HUMAN Y-21 TRANSLOCATION CHROMOSOME

A de novo dicentric Y;21 (q11.23;p11) translocation chromosome with on e of its two centromeres inactive has provided the opportunity to stud y the relationship between centromeric inactivation, the organization of alphoid satellite DNA and the distribution of CENP-C. The proband, a male with minor features of Down's syndrome, had a major cell line w ith 45 chromosomes including a single copy of the translocation chromo some, and a minor one with 46 chromosomes including two copies of the translocation chromosome and hence effectively trisomic for the long a rm of chromosome 21. Centromeric activity as defined by the primary co nstriction was variable: in most cells with a single copy of the Y;21 chromosome, the Y centromere was inactive. In the cells with two copie s, one copy had an active Y centromere (chromosome 21 centromere inact ive) and the other had an inactive Y centromere (chromosome 21 centrom ere active). Three different partial deletions of the Y alphoid array were found in skin fibroblasts and one of these was also present in bl ood. Clones of single cell origin from fibroblast cultures were analys ed both for their primary constriction and to characterise their alpho id array. The results indicate that (1) each clone showed a fixed patt ern of centromeric activity; (2) the alphoid array size was stable wit hin a clone; and (3) inactivation of the Y centromere was associated w ith both full-sized and deleted alphoid arrays. Selected clones were a nalysed with antibodies to CENP-C, and staining was undetectable at bo th intact and deleted arrays of the inactive Y centromeres. Thus centr omeric inactivation appears to be largely an epigenetic event.