Bennani-Baiti I M, Jones B K, Liebhaber S A, Cooke N E
Department of Genetics, Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Genomics. 1995 Oct 10;29(3):647-52. doi: 10.1006/geno.1995.9954.
The human growth hormone (GH) locus, a cluster of five genes, spans 47 kb on chromosome 17q22-q24. The skeletal muscle sodium channel alpha-subunit locus (SCN4A), a 32.5-kb gene, has previously been mapped to 17q23.1-q25.3. We demonstrate that both the GH gene cluster and the SCN4A gene colocalize to a single 525-kb yeast artificial chromosome (YAC) containing DNA derived from human chromosome 17. Restriction maps of two cosmids encompassing the 5' terminus of the GH locus and including up to 40 kb of 5'-flanking sequences demonstrate a perfect 20-kb overlap with previously published maps of the SCN4A gene. A 720-bp DNA segment, 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 that the SCN4A gene and the entire GH gene cluster are contained within 100 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.
人类生长激素（GH）基因座由五个基因组成，位于17号染色体q22 - q24区域，跨度为47 kb。骨骼肌钠通道α亚基基因座（SCN4A）是一个32.5 kb的基因，此前已定位到17q23.1 - q25.3。我们证明，GH基因簇和SCN4A基因共定位于一个单一的525 kb酵母人工染色体（YAC）上，该YAC包含源自人类17号染色体的DNA。两个黏粒的限制酶切图谱涵盖了GH基因座的5'末端，并包括多达40 kb的5'侧翼序列，显示与先前发表的SCN4A基因图谱有20 kb的完美重叠。对一个7２0 bp的DNA片段进行了测序，该片段包含GH基因5'端32.3至31.6 kb的序列，发现其与SCN4A基因的第14外显子相同。这些数据表明，SCN4A基因和整个GH基因簇位于17号染色体上100 kb的范围内，且仅相隔21.5 kb。值得注意的是，GH和SCN4A之间的这种物理连锁还表明，对GH基因组织特异性转录激活至关重要的多个元件位于SCN4A基因内。
