Analysis of heritable variation in the human growth hormone(HGH)/human placental lactogen(HPL) gene cluster

Abstract

Cellular DNA from 30 normal and 19 hypopituitary subjects was studied to determine whether heritable HGH deficiency is due to alteration in the HGH/HPL gene cluster on human chromosome 17. Subjects included 5 with multiple pituitary hormone deficiency, 3 with bioinactive HGH, 8 with isolated HGH deficiency without affected siblings and 2 pairs of siblings with autosomal recessive isolated HGH deficiency. DNA fragments containing HGH and HPL-related gene sequences were detected by Southern blot hybridization to a 32p-labeled HPL cDNA probe. HGH and HPL genes exist in multiple, non-allelic forms. They are not resolved in Eco RI digests but can be distinguished in Bam HI and Bgl II digests. We have detected 3 variant polymorphic Bgl II restriction patterns which are traceable through pedigrees and can be used to test for physical linkage of HGH deficiency to HGH/HPL gene cluster variation. All HGH/HPL restriction patterns found in hypopituitary individuals were also found in normals. Thus, there were no instances in which HGH deficiency could be attributed to deletion of an HGH gene. Also, discordance for Bgl II restriction patterns in 2 siblings with autosomal recessive HGH deficiency provided evidence against HGH gene mutation as the cause of the disease.