In situ hybridization mapping of human chromosome 16: evidence for a high frequency of repetitive DNA sequences.

Fluorescence in situ hybridization (FISH) provides a rapid approach to regional localization of overlapping clone sets (contigs) developed by various fingerprinting approaches. We have used 70 cosmid clones derived from 48 different contigs, part of the developing contig map of chromosome 16 (Stallings et al., 1990, 1992a), to cytogenetically map an estimated 8.6 million base pairs (Mbp) of chromosome 16 DNA (approximately 8-9% total coverage). Although the majority of cosmid contigs hybridized to single sites on chromosome 16, a significant fraction (23%) hybridized to multiple regions on chromosome 16; a subset of these also hybridized to other human chromosomes. In most instances, clones that mapped to multiple locations were found to contain low-abundance repetitive DNA sequences. The FISH data presented here, coupled with published mapping data from somatic cell hybrids (Callen et al., 1992), permits independent verification of the integrity of chromosome 16 cosmid contigs. The order of clones derived by FISH agrees closely with the cell hybrid mapping data and can be correlated with chromosome bands and specific chromosomal translocation breakpoints.