THE UTROPHIN AND DYSTROPHIN GENES SHARE SIMILARITIES IN GENOMIC STRUCTURE

Utrophin and dystrophin are highly homologous proteins which are recip rocally expressed in DMD (Duchenne muscular dystrophy) muscle. The rem arkable similarity of these proteins suggests that they may play a sim ilar cellular role in some circumstances; if this were the case then u trophin may be capable of replacing dystrophin in DMD patients. In thi s paper we show that the genomic structure of the utrophin gene is sim ilar to the dystrophin gene, further exemplifying the relatedness of t he two genes and their gene products. We have constructed a 1.25Mb con tig of eight yeast artificial chromosome (YAC) clones covering the utr ophin gene located on chromosome 6q24. Utrophin is encoded by multiple small exons spanning approximately 900kb. The distribution of exons w ithin the genomic DNA has similarities to that of the dystrophin gene. In contrast to dystrophin, the utrophin gene has a long 5' untranslat ed region composed of two exons and a cluster of unmethylated, rare-cu tting restriction enzyme sites at the 5' end of the gene. Similarities between the genomic structure suggest that utrophin and dystrophin ar ose through an ancient duplication event involving a large region of g enomic DNA.