Sequence of the variant thyroxine-binding globulin of Australian aborigines. Only one of two amino acid replacements is responsible for its altered properties.
Open Access
- 1 April 1989
- journal article
- research article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 83 (4), 1344-1348
- https://doi.org/10.1172/jci114021
Abstract
A form of thyroxine-binding globulin (TBG) with reduced affinity for hormone and increased susceptibility to heat and acid denaturation has been identified in Australian Aborigines (TBG-A). Results of heat denaturation of TBG established that the TBGA allele is X linked and has a frequency of 50.9% in Western Australian Aborigines. The sequence of an isolated TBGA allele differed at two positions from that of the normal TBG allele (TBGC). One substitution was in codon 191, ACA (threonine) rather than GCA (alanine), and the other was in codon 283, TTT (phenylalanine) instead of TTG (leucine). These nucleotide substitutions resulted in the loss of sites for the enzymes Bgl 1 and Tth 111 II, respectively. The nucleotide substitutions in the TBG-A allele was confirmed by digestion of genomic DNA segments amplified using the polymerase chain reaction. The Bgl 1 and Tth 111 II sites were absent in the genes of two Aboriginal men expressing TBG-A and were present in those of three Aboriginal and six Caucasian males expressing TBG-C. The TBG gene of a seventh Caucasian male possessed the Bgl 1 site but had lost the Tth 111 II site; sequencing of this allele revealed only the substitution in codon 283 identical to that in the TBGA allele. As the biochemical properties of TBGPhe-283 expressed by this individual were indistinguishable from normal TBGLeu-283, we believe that the abnormal properties of TBG-A are due to substitution of alanine for threonine at residue 191.This publication has 14 references indexed in Scilit:
- Primer-Directed Enzymatic Amplification of DNA with a Thermostable DNA PolymeraseScience, 1988
- Complete amino acid sequence of human thyroxine-binding globulin deduced from cloned DNA: close homology to the serine antiproteases.Proceedings of the National Academy of Sciences, 1986
- Variant thyroxine-binding globulin in serum of Australian Aborigines: its physical, chemical and biological propertiesJournal of Endocrinological Investigation, 1985
- Characterization of Thyroxine-Binding Globulin Secreted by a Human Hepatoma Cell Line*Journal of Clinical Endocrinology & Metabolism, 1985
- X-Chromosome-Linked Inheritance of the Variant Thyroxine-Binding Globulin in Australian Aborigines*Journal of Clinical Endocrinology & Metabolism, 1985
- Effect of tunicamycin and monensin on secretion of thyroxine-binding globulin by cultured human hepatoma (Hep G2) cells.Journal of Biological Chemistry, 1984
- A possible variant of thyroxine-binding globulin in Australian AboriginesClinica Chimica Acta; International Journal of Clinical Chemistry, 1981
- Polymorphic DNA region adjacent to the 5' end of the human insulin gene.Proceedings of the National Academy of Sciences, 1981
- Distribution and Inheritance of Low Serum Thyroxine‐binding Globulin Levels in Australian Aborigines: A New Genetic VariationThe Medical Journal of Australia, 1980
- DNA sequencing with chain-terminating inhibitorsProceedings of the National Academy of Sciences, 1977