Many human genetic diseases are caused by only a minor mutation in a specific gene, such as a single-base mismatch (Cooper, et al., 1995). While sequence analysis of these genes provides a direct way of detecting genetic aberrations, it is at present too time consuming and expensive to be practical in broad-based diagnostic applications. The present invention provides a simple method for reliably, inexpensively and rapidly analyzing sequence alterations as minor as single base-pair mismatches in polynucleotide fragments derived from genes whose sequences are altered in a genetic disease.