skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Stop codon in the procollagen II gene (COL2A1) in a family with the Stickler syndrome (arthro-ophthalmopathy)

Abstract

Linkage analysis with restriction fragment length polymorphisms for the gene for type II procollagen (COL2A1) was carried out in a family with the Stickler syndrome, or arthro-ophthalmopathy, an autosomal dominant disorder that affects the eyes, ears, joints, and skeleton. The analysis demonstrated linkage of the disease and COL2A1 with a logarithm-of-odds score of 1.51 at zero recombination. A newly developed procedure for preparing cosmid clones was employed to isolate the allele for type II procollagen that was linked to the disease. Analysis of over 7000 nucleotides of the gene revealed a single base mutation that altered a CG dinucleotide and converted the codon CGA for arginine at amino acid position {alpha}1-732 to TGA, a stop codon. From previous work on procollagen biosynthesis, it is apparent that the truncated polypeptide synthesized from an allele with a stop codon at {alpha}1-732 cannot participate in the assembly of type II procollagen, and therefore that the mutation would decrease synthesis of type II procollagen. It was not apparent, however, why the mutation produced marked changes in the eye, which contains only small amounts of type II collagen, but relatively mild effects on the many cartilaginous structures of the body that are rich in themore » same protein.« less

Authors:
; ; ; ; ;  [1]; ;  [2]
  1. Thomas Jefferson Univ., Philadelphia, PA (United States)
  2. Wills Eye Hospital, Philadelphia, PA (United States)
Publication Date:
OSTI Identifier:
5701556
Resource Type:
Journal Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America; (United States)
Additional Journal Information:
Journal Volume: 88:15; Journal ID: ISSN 0027-8424
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; COSMIDS; DNA SEQUENCING; HEREDITARY DISEASES; ETIOLOGY; CODONS; COLLAGEN; DNA HYBRIDIZATION; DOMINANT MUTATIONS; EYES; FIBROBLASTS; GENETIC MAPPING; OLIGONUCLEOTIDES; RETINA; RFLPS; ANIMAL CELLS; BODY; BODY AREAS; CONNECTIVE TISSUE CELLS; DISEASES; FACE; HEAD; HYBRIDIZATION; MAPPING; MUTATIONS; NUCLEIC ACIDS; ORGANIC COMPOUNDS; ORGANS; PROTEINS; SCLEROPROTEINS; SENSE ORGANS; SOMATIC CELLS; STRUCTURAL CHEMICAL ANALYSIS; 550400* - Genetics

Citation Formats

Ahmad, N N, Ala-Kokko, L, Knowlton, R G, Jimenez, S A, Weaver, E J, Prockop, D J, Maguire, J I, and Tasman, W. Stop codon in the procollagen II gene (COL2A1) in a family with the Stickler syndrome (arthro-ophthalmopathy). United States: N. p., 1991. Web. doi:10.1073/pnas.88.15.6624.
Ahmad, N N, Ala-Kokko, L, Knowlton, R G, Jimenez, S A, Weaver, E J, Prockop, D J, Maguire, J I, & Tasman, W. Stop codon in the procollagen II gene (COL2A1) in a family with the Stickler syndrome (arthro-ophthalmopathy). United States. https://doi.org/10.1073/pnas.88.15.6624
Ahmad, N N, Ala-Kokko, L, Knowlton, R G, Jimenez, S A, Weaver, E J, Prockop, D J, Maguire, J I, and Tasman, W. 1991. "Stop codon in the procollagen II gene (COL2A1) in a family with the Stickler syndrome (arthro-ophthalmopathy)". United States. https://doi.org/10.1073/pnas.88.15.6624.
@article{osti_5701556,
title = {Stop codon in the procollagen II gene (COL2A1) in a family with the Stickler syndrome (arthro-ophthalmopathy)},
author = {Ahmad, N N and Ala-Kokko, L and Knowlton, R G and Jimenez, S A and Weaver, E J and Prockop, D J and Maguire, J I and Tasman, W},
abstractNote = {Linkage analysis with restriction fragment length polymorphisms for the gene for type II procollagen (COL2A1) was carried out in a family with the Stickler syndrome, or arthro-ophthalmopathy, an autosomal dominant disorder that affects the eyes, ears, joints, and skeleton. The analysis demonstrated linkage of the disease and COL2A1 with a logarithm-of-odds score of 1.51 at zero recombination. A newly developed procedure for preparing cosmid clones was employed to isolate the allele for type II procollagen that was linked to the disease. Analysis of over 7000 nucleotides of the gene revealed a single base mutation that altered a CG dinucleotide and converted the codon CGA for arginine at amino acid position {alpha}1-732 to TGA, a stop codon. From previous work on procollagen biosynthesis, it is apparent that the truncated polypeptide synthesized from an allele with a stop codon at {alpha}1-732 cannot participate in the assembly of type II procollagen, and therefore that the mutation would decrease synthesis of type II procollagen. It was not apparent, however, why the mutation produced marked changes in the eye, which contains only small amounts of type II collagen, but relatively mild effects on the many cartilaginous structures of the body that are rich in the same protein.},
doi = {10.1073/pnas.88.15.6624},
url = {https://www.osti.gov/biblio/5701556}, journal = {Proceedings of the National Academy of Sciences of the United States of America; (United States)},
issn = {0027-8424},
number = ,
volume = 88:15,
place = {United States},
year = {Thu Aug 01 00:00:00 EDT 1991},
month = {Thu Aug 01 00:00:00 EDT 1991}
}