OLIGONUCLEOTIDE PROBES FOR ALPHA-SATELLITE DNA VARIANTS CAN DISTINGUISH HOMOLOGOUS CHROMOSOMES BY FISH

Chromosomal heteromorphisms have been used extensively to mark individ ual chromosomes, However, classical banding techniques used to identif y these structural variants are imprecise and difficult to quantify, D ifferent chromosomes 17 from the human population are characterized by distinct haplotypes of alpha satellite DNA, We have used these sequen ce variants to construct oligonucleotide probes for fluorescence in si tu hybridization (FISH), These oligomers are the first reported FISH p robes 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 pol ymorphic marker, Furthermore, extended chromatin fiber techniques reve al the presence of discrete domains of different sequence variants wit hin individual centromeres, Extension of this strategy to create a bat tery of other variant-specific oligoprobes should provide a powerful d iagnostic tool for parent of origin effects in the study of aneuploidy , imprinting and cancer cytogenetics.