Premature chain termination is a unifying mechanism for COL1A1 null alleles in osteogenesis imperfecta type I cell strains

Journal Article · Tue Oct 01 04:00:00 EDT 1996 · American Journal of Human Genetics

OSTI ID:476749

Willing, M C; Deschenes, S P; Roberts, E J ^[1]

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1. Univ. of Iowa, Iowa City, IA (United States); and others

Nonsense and frameshift mutations, which predict premature termination of translation, often cause a dramatic reduction in the amount of transcript from the mutant allele (nonsense-mediated mRNA decay). In some genes, these mutations also influence RNA splicing and induce skipping of the exon that contains the nonsense codon. To begin to dissect how premature termination alters the metabolism of RNA from the COL1A1 gene, we studied nonsense and frameshift mutations distributed over exons 11-49 of the gene. These mutations were originally identified in 10 unrelated families with osteogenesis imperfecta (OI) type I. We observed marked reduction in steady-state amounts of mRNA from the mutant allele in both total cellular and nuclear RNA extracts of cells from affected individuals, suggesting that nonsense-mediated decay of COL1A1 RNA is a nuclear phenomenon. Position of the mutation within the gene did not influence this observation. None of the mutations induced skipping of either the exon containing the mutation or, for the frameshifts, the downstream exons with the new termination sites. Our data suggest that nonsense and frameshift mutations throughout most of the COL1A1 gene result in a null allele, which is associated with the predictable mild clinical phenotype, OI type I. 42 refs., 6 figs., 1 tab.

• OSTI ID: 476749
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 4 Vol. 59; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
CODONS
COLLAGEN
DNA-CLONING
DOMINANT MUTATIONS
EXONS
GENE MUTATIONS
HEREDITARY DISEASES
MESSENGER-RNA
METABOLISM
PATIENTS
PHENOTYPE
POLYMERASE CHAIN REACTION
RNA
SKELETAL DISEASES
SPLICING
TRANSCRIPTION