Rapid detection of human chromosome 21 aberrations by in situ hybridization

Plasmid clones containing up to 94 kilobases of single-copy DNA
from band q22.3 of chromosome 21 and a complete pool of insert DNA
from a chromosome 21 recombinant library have been used to rapidly
detect numerical and structural aberrations of chromosome 21 by in
situ hybridization in both metaphase and interphase cells. A
trisomic karyotype, diagnostic of Down syndrome, is readily
detected in nonmitotic cells because the majority of their nuclei
exhibit three discrete foci of hybridization, in contrast to normal
diploid cells, which show two foci. Chromosomal translocations
involving chromosome 21 sequences were also detected with these
probes, and the intranuclear location of 21q22.3 DNA sequences in
"normal" human brain neurons was established with the plasmid DNA
probe set. These results suggest that chromosome 21-specific probes
may have utility in clinical diagnostics, especially by
facilitating the direct analysis of interphase cells.