INCREASING THE INFORMATION-CONTENT OF STS-BASED GENOME MAPS - IDENTIFYING POLYMORPHISMS IN MAPPED STSS

Physical maps of the human genome are being constructed by many groups using a mapping strategy that relies on the development of sequence-t agged sites (STSs). Thousands of physically mapped STSs, representing hundreds of kilobases (kb) of unique human DNA sequence, have been gen erated by these efforts. Since sequence variations are found every 1-2 kb in the genome, it is possible to extract additional information fr om mapped STSs by scanning them for variations. By screening 154 of th e STSs published by the Whitehead Institute/MIT Genome Center, we have identified 47 new DNA sequence polymorphisms among the 37.2 kb of uni que DNA sequence contained in these STSs. Using a sequence-based appro ach to estimate allele frequencies for these variations, 29 of the sub stitution polymorphisms (1 in 1.3 kb) were found to have heterozygosit ies exceeding 32%. Our study shows that the information content of STS -based genome maps can be increased with minimal additional effort by scanning for DNA polymorphisms, and that ambiguities and errors in the initial STS sequence can be resolved and corrected in the process. (C ) 1996 Academic Press, Inc.