Abstract
Collagens IX and XI are quantitatively minor components of
the collagen fibrils in cartilage. The spectrum of the phenotypes
caused by mutations in the COL2A1 gene coding for collagen II, the
main cartilage collagen, is relatively well defined, but there is
little data on the phenotypes caused by collagen IX and XI mutations.
The structure of the human COL11A1 gene coding for the 1
chain of collagen XI was characterized here. It was found to consist
of 68 exons and span 160 kb, excluding introns 1 and 4. Over 50
kb of new intronic sequences were defined. The exon-intron organization
coding for the major triple helical domain was found to be identical
to that of the human COL11A2 gene, which codes for the 2
chain of collagen XI.
The sensitivity of conformation sensitive gel electrophoresis
(CSGE) for mutation detection was improved and tested with a large
number of sequence variations in collagen genes. The sensitivity with
the revised conditions was found to be close to 100%. In
addition, CSGE was found to be a simple and practical method for
analyzing large numbers of samples.
Fifteen mutations in the COL11A1 gene and eight in the COL2A1
gene were found by CSGE in patients with Marshall or Stickler syndrome.
The genotypic-phenotypic comparison indicated that mutations leading
to a premature translation termination codon in the COL2A1 gene
resulted in Stickler syndrome and splicing mutations of 54 bp exons
in the C terminal half of the COL11A1 gene resulted in Marshall
syndrome. The other COL11A1 mutations caused phenotypes overlapping
both syndromes.
In an analysis of the COL9A2 gene in 157 patients with intervertebral
disc disease, six were found to have a tryptophan for glutamine
substitution in the central collagenous domain of the collagen IX molecule.
None of 174 control individuals had this substitution. The substitution
cosegregated with the phenotype in the families studied, and linkage
and linkage disequilibrium analyses supported the association of
the locus and the disease with a joint lod score of over 11.
| Identifer | oai:union.ndltd.org:oulo.fi/oai:oulu.fi:isbn951-42-5413-9 |
| Date | 13 October 1999 |
| Creators | Annunen, S. (Susanna) |
| Publisher | University of Oulu |
| Source Sets | University of Oulu |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/doctoralThesis, info:eu-repo/semantics/publishedVersion |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess, © University of Oulu, 1999 |
| Relation | info:eu-repo/semantics/altIdentifier/pissn/0355-3221, info:eu-repo/semantics/altIdentifier/eissn/1796-2234 |
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