Centromeric association of small supernumerary marker chromosomes with their sister-chromosomes detected by three dimensional molecular cytogenetics

Here we present the first three-dimensional interphase fluorescence in situ hybridization (FISH) studies for the nuclear architecture of sSMC. It could be shown that sSMC derived from chromosomes 15, 16 or 18 preferentially colocalized with one of their corresponding sister chromosomes. This was true in B- and T-lymphocytes as well as in skin fibroblasts. Additionally, a case with a complex sSMC with a karyotype 47,XY,+der(18)t(8;18)(8p23.2 ~ 23.1;18q11.1) was studied. Here the sSMC co-localized with one homologous chromosome 8 instead of 18.Overall, there is a kind of "attraction" between an sSMC and one of its homologous sister chromosomes. This seems to be transmitted by the euchromatic part of the sSMC rather than its heterochromatic one.Small supernumerary marker chromosomes (sSMC) are reported in 0.043% of newborn infants, 0.077% of prenatal cases, 0.433% of mentally retarded patients and 0.171% of subfertile people [1]. They are defined as structurally abnormal chromosomes that cannot be identified or characterized unambiguously by conventional banding cytogenetics alone, and are generally equal in size or smaller than a chromosome 20 of the same metaphase spread. sSMC are mostly detected unexpectedly in routine cytogenetics [2] and are not easy to correlate with a specific clinical outcome [3]. It is known that ~30% of sSMC are derived from chromosome 15; ~11% are i(12p)-, i.e. Pallister-Killian-, ~10% are der(22)-, ~7% are inv dup (22)-cat-eye- and ~6% are i(18p)-syndrome associated sSMC [2]. Also essential progress towards genotype-phenotype-correlation was recently achieved [4,5].Still little is known on the biology of sSMC in terms of formation [2,6], centromeric activity in dicentric sSMC [7], mitotic and meiotic stability [3] and coexistence of sSMC and uniparental disomy [8], or positioning of an sSMC in the interphase nucleus. Especially for the latter problem there were up to now only 'indirect' studies done, i.e. spread metaphases were analyzed to