The β subunit of human chorionic gonadotropin is encoded by multiple genes

Two recombinant phage clones bearing sequences corresponding to the β subunit of human chorionic gonadotropin (hCGβ) were isolated from a human genomic library. The β sequences were mapped by blot hybridization of restriction digests of these phage DNAs and the nonoverlapping inserts were subcloned in pBR322 and sequenced. The nucleotide-sequencing data show that the hCGβ subunit is encoded by at least three nonallelic genes. Moreover, based on restriction analyses of human placental DNA, these genes may be linked in a single cluster with four other hCGβ-like genes. The sequenced genes all differ in their 5' flanking regions, and none of them is completely homologous in sequence to either of two hCGβ cDNA clones used here. In the translated region of one of these genes, three base substitutions result in two changes from the reported amino acid sequence. In the family of β-containing glycoprotein hormones, the hCGβ subunit is unique in that it contains an extension of 29 amino acids at its COOH end. The DNA sequence corresponding to this region in the sequenced genes is part of a larger exon. These data show that the COOH-terminal extension does not result from splicing of the primary RNA transcript.