The dachshund mutation

Last August, a study by Heidi Parker, Elaine Ostrander and colleagues in Bethesda, USA reported that a genetic mutation is responsible for short legs in dogs. The finding adds to the understanding of growth control and general genetic mechanisms. 

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Examples of short-legged (chondrodysplastic) and normal-legged dogs

The scientists compared the genes of 835 dogs from 76 different breeds with short and long legs. They found a mutation that is associated with short legs – a gene duplication of fgf4. This gene, with the full name fibroblast growth factor 4 is controlling growth in mammals and is also responsible for some forms of dwarfism in humans.

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Association between short legs and different  gene forms. The peak on chromosome 18 is the  fgf4 duplication.

When analyzing the reason of the mutation the scientists were surprised to find that is due to so called retrotransposition. That occurs when the messenger form of the gene, the one that is used to make a protein, is inserted into a different place.

retrotransposon

The mechanism of retrotransposition: A mammalian gene is usually made of elements that contain information about the structure of a protein –  they are called exons and shown here as thick patches. Other parts of the gene do not contain information about the structure of the protein but can control when the protein is being made, like the part of DNA before the first exon. These parts are not present on the intermediate form between gene and protein – the mRNA. Because the template of gene duplication in retrotransposition is the mRNA, the regulatory parts do not get copied to the new location.  Therefore it is thought that the new gene can not serve to make a protein. This study shows that it can, when it uses regulatory elements that are coincidentally present at the new location.

We carry many such gene duplications. But it was thought that they are not making proteins, because they lack the regulatory parts necessary. But this study gives an example that the copied gene can probably use new regulatory elements close to the part of which it was inserted. And because these are different from the original ones, the gene now makes a protein at a different time and place in the developing animal – thereby giving rise to new traits – in this case the shape and length of the legs.

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