Mutations of the Gs alpha-subunit gene in Albright hereditary osteodystrophy detected by denaturing gradient gel electrophoresis.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 87 ·No. 21 ·1990-11-00 ·Pages 8287-90

Weinstein LS, Gejman PV, Friedman E, Kadowaki T, Collins RM, Gershon ES, Spiegel AM

Abstract

Affected members of most kindreds with Albright hereditary osteodystrophy have a partial deficiency of functional Gs, the guanine nucleotide-binding protein that stimulates adenylyl cyclase. By use of the polymerase chain reaction to amplify genomic fragments with the attachment of a high-melting G + C-rich region (GC clamp) and analysis of these fragments by denaturing gradient gel electrophoresis, heterozygous mutations in the Gs alpha-subunit gene were found in two kindreds. These included a G----C substitution at the donor splice junction of intron 10 and a coding frameshift created by a single base deletion within exon 10. The findings illustrate the heterogeneity of genetic defects in Albright hereditary osteodystrophy and the usefulness of the polymerase chain reaction-denaturing gradient gel electrophoresis method to search rapidly for mutations in a large candidate gene.

MeSH Terms

Amino Acid Sequence Base Sequence Cells, Cultured DNA/genetics,isolation & purification Female Frameshift Mutation GTP-Binding Proteins/genetics Genes Humans Macromolecular Substances Male Molecular Sequence Data Oligonucleotide Probes/chemical synthesis Pedigree Polymerase Chain Reaction Pseudohypoparathyroidism/genetics Reference Values

Chemicals

Macromolecular Substances Oligonucleotide Probes DNA GTP-Binding Proteins

Authors & Affiliations

7 authors, click to expand affiliations / ORCID

Weinstein L S

Molecular Pathophysiology Branch, National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, MD 20892.

Gejman P V

Friedman E

Kadowaki T

Collins R M

Gershon E S

Spiegel A M

References (30)

30 references, click to expand

Pseudohypoparathyroidism: report on a family with four affected sisters.
Arch Intern Med. 1979 Feb;139(2):204-7 PMID: 219790
Pseudo-pseudohypoparathyroidism.
Trans Assoc Am Physicians. 1952;65:337-50 PMID: 13005676
Defect of receptor-cyclase coupling protein in psudohypoparathyroidism.
N Engl J Med. 1980 Jul 31;303(5):237-42 PMID: 6247654
Deficiency of hormone receptor-adenylate cyclase coupling protein: basis for hormone resistance in pseudohypoparathyroidism.
Am J Physiol. 1982 Jul;243(1):E37-42 PMID: 6283911
Specific transcription and RNA splicing defects in five cloned beta-thalassaemia genes.
Nature. 1983 Apr 14;302(5909):591-6 PMID: 6188062
Modification of the melting properties of duplex DNA by attachment of a GC-rich DNA sequence as determined by denaturing gradient gel electrophoresis.
Nucleic Acids Res. 1985 May 10;13(9):3111-29 PMID: 2987873
Nearly all single base substitutions in DNA fragments joined to a GC-clamp can be detected by denaturing gradient gel electrophoresis.
Nucleic Acids Res. 1985 May 10;13(9):3131-45 PMID: 4000972
Activity of the stimulatory guanine nucleotide-binding protein is reduced in erythrocytes from patients with pseudohypoparathyroidism and pseudopseudohypoparathyroidism: biochemical, endocrine, and genetic analysis of Albright's hereditary osteodystrophy in six kindreds.
J Clin Endocrinol Metab. 1986 Mar;62(3):497-502 PMID: 3003142
Signal transduction by guanine nucleotide binding proteins.
Mol Cell Endocrinol. 1987 Jan;49(1):1-16 PMID: 2435586
G proteins: transducers of receptor-generated signals.
Annu Rev Biochem. 1987;56:615-49 PMID: 3113327
Reduced expression of multiple forms of the alpha subunit of the stimulatory GTP-binding protein in pseudohypoparathyroidism type Ia.
Proc Natl Acad Sci U S A. 1987 Oct;84(20):7266-9 PMID: 2890163
A rapid method for the purification of DNA from blood.
Nucleic Acids Res. 1987 Nov 25;15(22):9611 PMID: 3684611
Computational simulation of DNA melting and its application to denaturing gradient gel electrophoresis.
Methods Enzymol. 1987;155:482-501 PMID: 2828875
Detection and localization of single base changes by denaturing gradient gel electrophoresis.
Methods Enzymol. 1987;155:501-27 PMID: 3431470
Genetic deficiency of the alpha subunit of the guanine nucleotide-binding protein Gs as the molecular basis for Albright hereditary osteodystrophy.
Proc Natl Acad Sci U S A. 1988 Jan;85(2):617-21 PMID: 2829196
Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase.
Science. 1988 Jan 29;239(4839):487-91 PMID: 2448875
Isolation and characterization of the human Gs alpha gene.
Proc Natl Acad Sci U S A. 1988 Apr;85(7):2081-5 PMID: 3127824
Splice junction mutation in some Ashkenazi Jews with Tay-Sachs disease: evidence against a single defect within this ethnic group.
Proc Natl Acad Sci U S A. 1988 Jun;85(11):3955-9 PMID: 3375249
G protein multiplicity in eukaryotic signal transduction systems.
Biochemistry. 1988 Jul 12;27(14):4957-65 PMID: 3139030
Donor splice site mutation in the apolipoprotein (Apo) C-II gene (Apo C-IIHamburg) of a patient with Apo C-II deficiency.
J Clin Invest. 1988 Nov;82(5):1489-94 PMID: 3263393
Attachment of a 40-base-pair G + C-rich sequence (GC-clamp) to genomic DNA fragments by the polymerase chain reaction results in improved detection of single-base changes.
Proc Natl Acad Sci U S A. 1989 Jan;86(1):232-6 PMID: 2643100
A 5' splice-region G----C mutation in exon 1 of the human beta-globin gene inhibits pre-mRNA splicing: a mechanism for beta+-thalassemia.
Proc Natl Acad Sci U S A. 1989 Feb;86(3):1041-5 PMID: 2915972
The use of denaturing gradient gel electrophoresis to screen for DNA sequence polymorphisms in the human factor VIII gene.
Electrophoresis. 1989 May-Jun;10(5-6):390-6 PMID: 2569966
Laron dwarfism and mutations of the growth hormone-receptor gene.
N Engl J Med. 1989 Oct 12;321(15):989-95 PMID: 2779634
Factor XI (plasma thromboplastin antecedent) deficiency in Ashkenazi Jews is a bleeding disorder that can result from three types of point mutations.
Proc Natl Acad Sci U S A. 1989 Oct;86(20):7667-71 PMID: 2813350
Identification of the multiple beta-thalassemia mutations by denaturing gradient gel electrophoresis.
J Clin Invest. 1990 Feb;85(2):550-3 PMID: 2298920
A nonsense mutation causing decreased levels of insulin receptor mRNA: detection by a simplified technique for direct sequencing of genomic DNA amplified by the polymerase chain reaction.
Proc Natl Acad Sci U S A. 1990 Jan;87(2):658-62 PMID: 2300553
Use of denaturing gradient gel electrophoresis to detect point mutations in the factor VIII gene.
Genomics. 1990 Feb;6(2):293-301 PMID: 2106480
Mutation in the gene encoding the stimulatory G protein of adenylate cyclase in Albright's hereditary osteodystrophy.
N Engl J Med. 1990 May 17;322(20):1412-9 PMID: 2109828
Two-dimensional electrophoretic separation of restriction enzyme fragments of DNA.
Methods Enzymol. 1979;68:183-91 PMID: 232212

Article Info

Journal

Proceedings of the National Academy of Sciences of the United States of America

Abbr.

Proc Natl Acad Sci U S A

ISSN

0027-8424

DOI

10.1073/pnas.87.21.8287

Published

1990-11-00

Pages

8287-90

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC54940

Subset

External Links

PubMed source DOI: 10.1073/pnas.87.21.8287 PMC Full Text View journal details

Analysis Services

Mutations of the Gs alpha-subunit gene in Albright hereditary osteodystrophy detected by denaturing gradient gel electrophoresis.

Contact

WeChat Official Account