Characterization and mapping of four novel human expressed polymorphic trinucleotide microsatellites

Recently, several important human genetic diseases have been shown to be du e to pathological expansion of expressed trinucleotide microsatellites. Dis covery of other such 'expansion diseases' will depend on characterization o f more expressed loci containing trinucleotide repeats. We searched the exp ressed sequence tag database (dbEST) for repetitive trinucleotides and sele cted four loci for further studies (EST00586 EST05486, EST13299 and HHEA48B ). For each locus, we have identified size polymorphism by PCR amplificatio n and achieved chromosomal mapping using a somatic hybrid cell panel and th e Stanford G3 radiation hybrid panel. Further searches of GenBank, dbEST an d UniGene unraveled EST clusters for three of the loci, allowing constructi on of contigs and, in one instance, identification of a partial open readin g frame. Three of the loci were linked to autosomal dominant human genetic diseases whose primary gene defect has not yet been established. Although i t is a priori improbable that there is an etiological connection between th e loci studied and the diseases, our results demonstrate that dbEST constit utes a useful starting point in the search for candidate loci for new expan sion diseases. (C) 1998 Elsevier Science B.V. All rights reserved.