HUMAN MUCIN GENE MUC4 - ORGANIZATION OF ITS 5'-REGION AND POLYMORPHISM OF ITS CENTRAL TANDEM REPEAT ARRAY

In a previous study we isolated a partial cDNA with a tandem repeat of 48 bp, which allowed us to map a novel human mucin gene named MUC4 to chromosome 3q29. Here we report the organization and sequence of the 5'-region and its junction with the tandem repeat array of MUC4. Analy sis of three overlapping genomic clones allowed us to obtain a partial restriction map of MUC4 and to locate the complete 48 bp tandem repea t domain on a PstI/EcoRI genomic fragment that exhibits a very large v ariation in number of tandem repeats (7-19 kb). cDNA clonal extension allowed us to obtain the entire 5' coding region of MUC4. Exon 1 consi sts of a 5' untranslated region and an 82 bp fragment encoding the sig nal peptide. This latter shows a high degree of similarity to the sign al peptide of another apomucin, ASGP-1. Exon 2 is extremely large and contains a unique sequence that is followed by the whole tandem repeat domain. It encodes only one cysteine residue, making MUC4 different f rom mucin genes belonging to the 11p15.5 family. Moreover, an intron d ownstream from the tandem repeat array consists mainly of a 15 bp tand em repeat that exhibits a polymorphism in having a variable number of tandem repeats.