PHYSICAL LINKAGE OF THE HUMAN GROWTH-HORMONE GENE-CLUSTER AND THE SKELETAL-MUSCLE SODIUM-CHANNEL ALPHA-SUBUNIT GENE (SCN4A) ON CHROMOSOME-17

The human growth hormone (GH) locus, a cluster of five genes, spans 47 kb on chromosome 17q22-q24. The skeletal muscle sodium channel cu-sub unit locus (SCN4A), a 32.5-kb gene, has previously been mapped to 17q2 3.1-q25.3. We demonstrate that both the GH gene cluster and the SCN4A gene colocalize to a single 525-kb yeast artificial chromosome (YAC) c ontaining DNA derived from human chromosome 17. Restriction maps of tw o cosmids encompassing the 5' terminus of the GH locus and including u p to 40 kb of 5'-flanking sequences demonstrate a perfect 20-kb overla p with previously published maps of the SCN4A gene. A 720-bp DNA segme nt, encompassing sequences 32.3 to 31.6 kb 5' to GH, was sequenced and found to be identical to exon 14 of SCN4A. These data demonstrate tha t the SCN4A gene and the entire GH gene cluster are contained within 1 00 kb on chromosome 17 and are separated by only 21.5 kb. Remarkably, this physical linkage between GH and SCN4A also reveals that multiple elements critical to tissue-specific transcriptional activation of the GH gene lie within the SCN4A gene. (C) 1995 Academic Press, Inc.