Stop codon in the procollagen II gene (COL2A1) in a family with the Stickler syndrome (arthro-ophthalmopathy)
- Thomas Jefferson Univ., Philadelphia, PA (United States)
- Wills Eye Hospital, Philadelphia, PA (United States)
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.
- OSTI ID:
- 5701556
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 88:15; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
Similar Records
A fourth example suggests that premature termination codons in the COL2A1 gene are a common cause of the Stickler syndrome: Analysis of the COL2A1 gene by denaturing gradient gel electrophoresis
Analysis of four families with the Stickler syndrome by linkage studies. Identification of a new premature stop codon in the COL2A1 gene in a family
Related Subjects
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