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Human Molecular Genetics, Vol 5, 1793-1799, Copyright © 1996 by Oxford University Press

ARTICLES

Oligonucleotide probes for alpha satellite DNA variants can distinguish homologous chromosomes by FISH

CL O'Keefe, PE Warburton and AG Matera
Department of Genetics, Case Western Reserve University and University Hospitals of Cleveland, OH 44106-4955, USA.

Chromosomal heteromorphisms have been used extensively to mark individual chromosomes. However, classical banding techniques used to identify these structural variants are imprecise and difficult to quantify. Different chromosomes 17 from the human population are characterized by distinct haplotypes of alpha satellite DNA. We have used these sequence variants to construct oligonuoleotide probes for fluorescence in situ hybridization (FISH). These oligomers are the first reported FISH probes that can discriminate between cytogenetically indistinguishable chromosome homologues. They have been used to follow the transmission of a single chromosome 17 through a pedigree, similar to a typical polymorphic marker. Furthermore, extended chromatin fiber techniques reveal the presence of discrete domains of different sequence variants within individual centromeres. Extension of this strategy to create a battery of other variant- specific oligoprobes should provide a powerful diagnostic tool for parent of origin effects in the study of aneuploidy, imprinting and cancer cytogenetics.
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