Constitutional aneuploidy in the normal human brain

The mouse brain contains genetically distinct cells that differ with respect to chromosome number manifested as aneuploidy (Rehen et al., 2001); however, the relevance to humans is not known. Here, using double- label fluorescence in situ hybridization for the autosome chromosome 21 ( chromosome 21 point probes combined with chromosome 21 " paint" probes), along with immunocytochemistry and cell sorting, we present evidence for chromosome gain and loss in the human brain. Chromosome 21 aneuploid cells constitute similar to 4% of the estimated one trillion cells in the human brain and include non- neuronal cells and postmitotic neurons identified by the neuron-specific nuclear protein marker. In comparison, human interphase lymphocytes present chromosome 21 aneuploidy rates of 0.6%. Together, these data demonstrate that human brain cells ( both neurons and non- neuronal cells) can be aneuploid and that the resulting genetic mosaicism is a normal feature of the human CNS.