ABSTRACT
Nuclear DNA from individuals belonging to nine different families in which two sibs were affected with isolated growth hormone deficiency type I were studied by restriction endonuclease analysis. By using 32P-labeled human growth hormone or the homologous human chorionic somatomammotropin complementary DNA (cDNA) sequences as a probe, the growth hormone genes of affected individuals from all families yielded normal restriction patterns. Polymorphic restriction endonuclease sites (HincII and MspI), which are closely linked to the structural gene for growth hormone on chromosome 17, were used as markers in linkage analysis of DNA of family members. Of the nine affected sib pairs two were concordant, three were possibly concordant, and four were discordant for both linked markers. Since only concordant sib pairs would have inherited the same growth hormone alleles, further studies to identify mutations of the growth hormone genes should be limited to this subgroup. It is unlikely that the discordance observed in four of the sib pairs is due to recombination, because the polymorphic HincII site is only 116 base-pairs from the -26 codon of the growth hormone gene. Thus, in at least four of the nine families, the mutation responsible for isolated growth hormone deficiency is not within or near the structural gene for growth hormone on chromosome 17.
Subject(s)
Growth Disorders/genetics , Growth Hormone/deficiency , Growth Hormone/genetics , Chromosome Mapping , DNA Restriction Enzymes , Genetic Linkage , Humans , Mutation , PedigreeABSTRACT
Analysis of GH gene structure in the mouse permits evolutionary comparisons with GH gene structure in the rat and provides information about the mechanism responsible for heritable deficiencies of anterior pituitary hormones. The little mutation in mice is analogous to autosomal recessive, isolated, partial deficiency of GH in man, whereas the Snell dwarf mutation is a model for autosomal recessive deficiency of GH, TSH, and PRL. Mouse cellular DNA was digested with the restriction enzymes Eco RI, Bam HI, Bgl II, Hind III, and Kpn I, singly and in combination. Gene sequences containing coding information for GH were detected by hybridization to a radiolabeled recombinant DNA probe complementary to a rat GH mRNA. The results of genomic restriction analysis indicate that there is a single type of mouse GH gene sequence per haploid genome with a length equal to or less than 32000 base pairs. The distances separating 6-base restriction sites close to the mouse GH gene differ from those close to the rat GH gene. A Kpn I site in the codons for amino acids 103 and 104 of rat GH is absent in the mouse gene. Restriction patterns of DNA from little and Snell dwarf mice did not differ from those of normal mice, indicating that these mutations do not involve deletions of the mouse GH gene.
Subject(s)
Genes , Growth Hormone/genetics , Hypopituitarism/genetics , Animals , Biological Evolution , Brain Chemistry , Cell Line , DNA/genetics , DNA Restriction Enzymes , DNA, Neoplasm/genetics , Heterozygote , Homozygote , Liver/analysis , Liver Neoplasms, Experimental/genetics , Mice , Nucleic Acid Hybridization , Pituitary Neoplasms/genetics , RatsSubject(s)
Infant, Newborn, Diseases/chemically induced , Povidone-Iodine/adverse effects , Povidone/analogs & derivatives , Thyroid Diseases/chemically induced , Administration, Topical , Humans , Infant, Newborn , Infant, Newborn, Diseases/blood , Infant, Newborn, Diseases/surgery , Male , Povidone-Iodine/administration & dosage , Thyroid Diseases/blood , Thyroid Function Tests , Thyrotropin/bloodABSTRACT
We have examined the human growth hormone (hGH) and human chorionic somatomammotropin (hCS) family of genes in genomic DNA from an individual with complete antenatal deficiency of hCS. Following digestion with a variety of bacterial restriction endonucleases, the DNA from this individual produced fewer fragments with homology to a radiolabeled hCS cDNA probe than did control DNA specimens. The patterns indicated that his DNA contained the normal hGH gene and an "hGH-like" gene, but lacked the hCS gene, a variant hGH gene, and another gene or genes with structural homology to hGH and hCS, which were present in all control DNA specimens. The findings were consistent with homozygosity for a gene deletion with a minimum length of 18.5 kb. Analysis of polymorphic restriction site variation related to the hGH and hCS gene cluster indicated that both parents and three older siblings were heterozygous for the deletion. The association between gene deletion and a normal growth pattern in this individual indicates that hCS and any other peptide hormones encoded by the variant hGH and the other related gene(s) that are deleted in this individual are not required for fetal or extrauterine growth.
Subject(s)
Chromosome Deletion , Placental Lactogen/deficiency , Adolescent , Adult , Child, Preschool , Female , Genes , Growth Hormone/deficiency , Growth Hormone/genetics , Heterozygote , Homozygote , Humans , Male , Pedigree , Placental Lactogen/genetics , PregnancyABSTRACT
Early exposure to benzo(a)pyrene, B(a(P, produces long-lasting effects on the cytochrome P-450 dependent monooxygenase system of rat liver microsomes. Adult male offspring of rats given B(a(P, 20 mg/kg i.p. during late pregnancy, showed either a small but significant depression of basal aryl hydrocarbon hydroxylase acitivity or an impaired induction response to B(a)P. Few significant changes were found in the relative amounts of the individual metabolites formed from B(a)P by microsomes from perinatally exposed rats, either in the basal or B(a)P-induced state. In addition, perinatal exposure to B(a)P tended to decrease the binding of B(a)P to calf thymus DNA in in vitro incubations.
