We have attempted to carry out a comparative study of chromosome 21 origin in DS children by molecular-cytogenetic [8] and cytogenetic [13,14] techniques. We found these approaches to be applicable in more than half (55.5%) of the families studied by FISH and 75% of fami­lies studied by the cytogenetic technique (Table 2). The combined application of FISH and cytogenetic techniques allows the detection of the origin of an additional chromo­some 21 with a high efficiency of 80.5%.

Heteromorphic regions of all human acrocentric chro­mosomes contain repetitive a-satellite DNA sequences. The existence of chromosome-specific satellite DNA se­quences and their relationship to heteromorphism of chro­mosome 21 have been demonstrated [6,8]. The variations of alphoid DNA in chromosome 21 are more extreme and could be arbitrarily classified into several discrete size classes [8]. Although, these variations are continuous, the proposed classification [8] allows semi-quantitative evalu­ation of centromeric heteromorphic alphoid DNA variants of chromosome 21.

The purpose of the present study was to verify the hypothesis that genetic variation in the alphoid DNA size on chromosome 21 is associated with a predisposition to non-disjunction. It has been hypothesized that extensive alphoid size differences between homologues of chromo­some 21 predisposed to non-disjunction [5]. The first at­tempt to identify the alphoid DNA variation in chromo­some 21 was carried out by radioactive in situ hybridiza­tion in 37 families with DS [6]. No correlation between non-disjunction and copy of alphoid DNA size was found. In the second attempt, using pulsed-field gel electrophore­sis, the chromosome 21 alphoid DNA array lengths in 23 families with an affected child with trisomy 21, were ex­amined [7]. An association between small alphoid size and maternal meiosis I was found. The evidence of the risk for non-disjunction is related to the small alphoid array size of one of the two chromosome 21 homologues. Thus, the data obtained in this field is rather contradictory.

We have attempted to find additional evidence of centromeric heteromorphic alphoid DNA variants of chro­mosome 21 correlating with non-disjunction using FISH and alphoid DNA chromosome 21-specific probes (aR1-6 specific to the a21-I array). We did not find any correla­tion between non-disjunction of chromosome 21 and al­phoid DNA variants revealed by FISH. The method we used [8] is semi-quantitative and does not allow accurate estimation of real alphoid DNA size due to restriction of the visual evaluation of FISH signal sizes. We can propose that the use of FISH in combination with quantitative computer-assisted approaches for evaluation of FISH re­sults should permit a more precise assessment of alphoid DNA variation and its possible involvement in non-dis­junction of chromosome 21.