Characterization and mapping of four novel human expressed polymorphic trinucleotide microsatellites

Recently, several important human genetic diseases have been shown to be due to pathological expansion of expressed trinucleotide microsatellites. Discovery of other such `expansion diseases' will depend on characterization of more expressed loci containing trinucleotide repeats. We searched the expressed sequence tag database (dbEST) for repetitive trinucleotides and selected four loci for further studies (EST00586 EST05486, EST13299 and HHEA48B). For each locus, we have identified size polymorphism by PCR amplification and achieved chromosomal mapping using a somatic hybrid cell panel and the Stanford G3 radiation hybrid panel. Further searches of GenBank, dbEST and UniGene unraveled EST clusters for three of the loci, allowing construction of contigs and, in one instance, identification of a partial open reading frame. Three of the loci were linked to autosomal dominant human genetic diseases whose primary gene defect has not yet been established. Although it is a priori improbable that there is an etiological connection between the loci studied and the diseases, our results demonstrate that dbEST constitutes a useful starting point in the search for candidate loci for new expansion diseases.