MOLECULAR TOPOGRAPHY OF THE SECONDARY CONSTRICTION REGION (QH) OF HUMAN CHROMOSOME-9 WITH AN UNUSUAL EUCHROMATIC BAND

Heterochromatin confined to pericentromeric (c) and secondary constric tion (qh) regions plays a major role in morphological variation of chr omosome 9, because of its size and affinity for pericentric inversion. Consequently, pairing at pachytene may lead to some disturbances betw een homologous chromosomes having such extreme variations and may resu lt in abnormalities involving bands adjacent to the qh region. We enco untered such a case, where a G-positive band has originated de novo, s uggesting a maternal origin from the chromosome 9 that has had a compl ete pericentric inversion. In previously reported cases, the presence of an extra G-positive band within the 9qh region has been familial, a nd in the majority of those cases it was not associated with any clini cal consequences. Therefore, this anomaly has been referred to as a '' rare'' variant. The qh region consists of a mixture of various tandeml y repeated DNA sequences, and routine banding techniques have failed t o characterize the origin of this extra genetic material. By the chrom osome in situ suppression hybridization technique using whole chromoso me paint, the probe annealed with the extra G-band, suggesting a euchr omatic origin from chromosome 9, presumably band p12. By the fluoresce nce in situ hybridization technique using alpha- and beta-satellite pr obes, the dicentric nature was further revealed, supporting the concep t of unequal crossing-over during maternal meiosis I, which could acco unt for a duplication of the h region. The G-positive band most likely became genetically inert when it was sandwiched between two blocks of heterochromatin, resulting in a phenotypically normal child. Therefor e, an earlier hypothesis, suggesting its origin from heterochromatin t hrough so-called euchromatinization, is refuted here. If the proband's progeny(ies) inherit this chromosome, it shall be envisaged as a rare familial variant whose clinical consequences remain obscure.