THE GENE FOR HUMAN U2 SNRNP AUXILIARY FACTOR SMALL 35-KDA SUBUNIT (U2AF1) MAPS TO THE PROGRESSIVE MYOCLONUS EPILEPSY (EPM1) CRITICAL REGIONON CHROMOSOME 21Q22.3

We used targeted exon trapping to clone portions of genes from human c hromosome 21q22.3. One trapped sequence showed complete homology with the cDNA of human U2AP(35) (M96982; HGM-approved nomenclature U2AF1), which encodes for the small 35-kDa subunit of the U2 snRNP auxiliary f actor. Using the U2AF1 cDNA as a probe, we mapped this gene to cosmid Q15D2, a P1, and YAC 350F7 of the Chumakov et al. (Nature 359: 380, 19 92) contig, close to the cystathionine-beta-synthase gene (CBS) on 21q 22.3, This localization was confirmed by PCR using oligonucleotides fr om the 3' UTR and by FISH. As UPAF1 associates with a number of differ ent factors during mRNA splicing, overexpression in trisomy 21 individ uals could contribute to some Down syndrome phenotypes by interfering with the splicing process. Furthermore, because this gene maps in the critical region for the progressive myoclonus epilepsy I locus (EPM1), mutation analysis will be carried out in patients to evaluate the pot ential role of U2AF1 as a candidate for EPM1. (C) 1996 Academic Press, Inc.