Human Molecular Genetics, Vol 6, 1729-1733, Copyright © 1997 by Oxford University Press
DJ Smith and EM Rubin
Libraries of the mammalian genome have generally been propagated in single
cells and have been used for gene discovery through in vitro analyses. We
have expanded upon this concept by the creation of panels of YAC transgenic
mice propagating targeted megabase regions of the genome. Such a panel of
mice can be called an 'in vivo library' and genes can be identified based
on functional screens of members of the library. To test this approach, we
created a 2 Mb in vivo library of human chromosome 21q22.2. Analysis of the
library has revealed that one 570 kb YAC, in two separate founder lines,
was associated with distinct learning deficits compared with the other
21q22 YAC transgenics and non- transgenic control animals. We have
localized the gene on the YAC that causes the deficits by taking advantage
of fragmentation of the YAC during the process of microinjection. The
responsible gene is the human minibrain gene, and the homolog of the gene
in Drosophila is also associated with learning defects. These results
suggest that altered dosage of minibrain is associated with abnormal neural
development in flies and mice and, in humans, may also be involved in the
molecular pathology of Down syndrome.
REVIEWS
Functional screening and complex traits: human 21q22.2 sequences affecting learning in mice
Human Genome Center, Lawrence Berkeley National Laboratory, CA 94720, USA. des@ux5.lbl.gov
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