Detection of chromosome aberrations in the human interphase nucleus by visualization of specific target DNAs with radioactive and non-radioactive in situ hybridization techniques: diagnosis of trisomy 18 with probe L1.84

The localization of chromosome 18 in human interphase nuclei is
demonstrated by use of radioactive and nonradioactive in situ
hybridization techniques with a DNA clone designated L1.84. This
clone represents a distinct subpopulation of the repetitive human
alphoid DNA family, located in the centric region of chromosome 18.
Under stringent hybridization conditions hybridization of L1.84 is
restricted to chromosome 18 and reflects the number of these
chromosomes present in the nuclei, namely, two in normal diploid
human cells and three in nuclei from cells with trisomy 18. Under
conditions of low stringency, cross-hybridization with other
subpopulations of the alphoid DNA family occurs in the centromeric
regions of the whole chromosome complement, and numerous
hybridization sites are detected over interphase nuclei. Detection
of chromosome-specific target DNAs by non-radioactive in situ
hybridization with appropriate DNA probes cloned from individual
chromosomal subregions presents a rapid means of identifying
directly numerical or even structural chromosome aberrations in the
interphase nucleus. Present limitations and future applications of
interphase cytogenetics are discussed.