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The human growth hormone locus: complete nucleotide sequence, evolution and expression of its genes

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Chen, E. Y., Liao, Y., Smith, D. H., Barrera−Saldaña, H. A., Gelinas, R. E., & Seeburg, P. H. (1989). The human growth hormone locus: complete nucleotide sequence, evolution and expression of its genes. Genomics, 4(4), 479-497.

The human chromosomal growth hormone locus contained on cloned DNA and spanning approximately 66,500 bp was sequenced in its entirety to provide a framework for the analysis of its biology and evolution. This locus evolved by a series of duplications and contains in its present form five genes which display a remarkably high degree of sequence identity (approximately 95%) in all their domains. The DNA sequence of the locus reveals the presence of 48 middle repetitive sequence elements of the Alu type and one member of the KpnI family, all located in the intergenic regions. The expression of each gene was examined by screening pituitary and placental cDNA libraries by using gene−specific oligonucleotides. According to this analysis, the hGH−N gene is transcribed exclusively in the pituitary, whereas the other four genes (hCS−L, hCS−A, hGH−V, hCS−B) are expressed only in placental tissue, at levels characteristic for each gene. Particular DNA sequences found upstream of the individual promoter regions might account for the observed tissue specificity and different transcriptional activity of the genes. The hCS−L gene carries a G to A transition in a sequence used by the other four genes as an intronic 5' splice donor site. This mutation results in a different splicing pattern and, hence, in a novel sequence of the hCS−L gene mRNA and the deduced polypeptide