Null Mutations in Type I
Collagen Genes
Null Mutations in Type I Collagen Genes Many null mutations lead to translation of a C-terminally truncated alpha chain, which does no longer contain the C-terminal nucleation site for triple helix formation. Other null mutations may decrease messenger RNA stability or may affect transcription or processing of messenger RNA. Dominant Negative Mutations in Type I Collagen Genes The majority (85%) of dominant negative mutations in type I collagen genes are due to replacements of one of the obligatory glycines in the alpha chains by a bigger amino acid. Since the bigger amino acid does not easily fit into the interior space of the triple helix, helix formation is temporarily halted. This pause in triple helix formation leads to over-modification of amino acids N-terminal to the mutation. Both the distortion in the triple helix and the over-modification of the alpha chains are believed to affect the structure and stability of the triple helix and the collagen fibrils.
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