Constitutional Aneuploidy in the Normal Human Brain

Chromosome 21 gain and loss is observed in cells isolated from the normal human brain. Human lymphocyte labeling demonstrates the specificity of the paint and point probes in metaphase spreads (A) and interphase nuclei (B). Neural progenitor cells from a Down's syndrome fetus have three copies of chromosome 21, as seen in a metaphase chromosome spread (C) and in an interphase nucleus (D), demonstrating the sensitivity of the FISH probes with regard to detecting numerical abnormalities of chromosome 21. E-H, Nuclei isolated from the brains of different patients containing one (E), two (F), three (G), or four (H) copies of chromosome 21. Blue indicates 4′,6-diamidino-2-phenylindole, whole-chromosome paint is shown in green, and the chromosome 21 point probe is shown in red. There is complete overlap between the paint and the point probe, as seen at higher magnification in the insets. Arrowheads indicate the numbers of chromosome 21 per cell. Scale bar, 5 μm.