Vol. 10, Issue 9, 1342-1350, September 2000

Alpha Satellite DNA Variant-Specific Oligoprobes Differing by a Single Base Can Distinguish Chromosome 15 Homologs

¹ Department of Genetics, ² Center for Human Genetics, and ³ Program in Cell Biology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio 44106-4955 USA

The ability to distinguish homologous chromosomes is a powerful cytogenetic tool. However, traditional techniques can only distinguish extreme physical variants and are highly dependent on sample preparation. We have previously reported oligonucleotide probes, specific for human chromosome 17 alpha satellite DNA sequence variants, that distinguish cytogenetically normal homologous chromosomes by FISH. Here we report the development of similar oligoprobes, differing at a single nucleotide position, that not only distinguish homologous chromosomes 15 but can be used to follow the transmission of a chromosome from parents to their offspring. We also identified a novel array-size polymorphism in another family. The alphoid array of one chromosome is quite small and below the detection threshold for our oligoprobes, although it is detectable by conventional FISH probes. This size polymorphism provides an additional FISH-based method for distinguishing homologs. Most importantly, this work illustrates the potential applicability of the technique to the entire human chromosome complement.

[The sequence data described in this paper have been submitted to the GenBank data library under accession nos. AF234768, AF234769, AF234770, AF234771, AF234772, AF2234773, AF234774, AF234775, AF234776, AF234777, and AF237720.]