Category Archives: Genetics

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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The contagious cancer

One of the first things a medical student learns about cancer is that it not a contagious disease. That this view doesn’t always hold true was proven by a study by Claudio Murgia, Robert Weiss and colleagues in 2006.

Cancers start with gene mutations in a cell of the body. The genes usually affected are important for the control of cell division – when they are damaged the cell escapes the control of the body and starts dividing aggressively, finally forming tumors that can invade and damage the organs and the whole organism. The reasons for the mutations are manifold: radiation, chemicals and microorganisms are among the culpable. And while these, like the virus causing Cervical cancer and the bacterium causing Stomach cancer, can be passed from person the person, it is not cancer itself, but its cause that is being transferred. The study of Mr Murgia showed for the first time that a type of cancer, Canine transmissible venereal tumor (CTVT) is exclusively passed by physical transfer of the cancer cells themselves.

For proving this, the London based scientists took DNA from cancer and normal cells of 40 dogs from 5 continents. When comparing the DNA samples, the researchers found that cancer cells are genetically different from their hosts and quite similar to each other. The researchers concluded that the different cancers are all progeny of a single cell that appeared more than 200 years ago. The cancer cells are being passed during sex.

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The proposed origin of CTVT

The study was the first to convincingly describe a contagious cancer. This January, another example of infectious cancer affecting Tasmanian devils was described by Elizabeth Murchison, Anthony Papenfuss and colleagues.

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A Tasmanian devil

The cancer is transmitted by biting and is highly aggressive, leading to death within months, threatening to extinguish Tasmanian devils in the wild within 50 years. The scientists hope that their results can lead to the development of a vaccine against the cancer cells.

The cloned dog from Korea

In 2005, the team of Woo Suk Hwang managed to clone the first dog – meaning to produce an individual that is genetically identical to another.

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Snuppy with his "father" on the left- the dog with which he shares his DNA. On the right is his surrogate mother – the dog that carried him in her womb, but didn’t contribute to any of his genes.

Hwang is infamous for faking his reports on allegedly producing human embryonic stem cells – after much investigation it turned out that on of the few reports that weren’t fake was the one about Snuppy, that’s how the afghan hound was named. Snuppy grew up to be a healthy dog and became a father in 2008.

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Snuppy with offspring

Meanwhile, Byeong-Chun Lee, the scientist who cloned Snuppy with Hwang has extended and improved his cloning technique. Since 2005 he has cloned wolves, beagles among others. He also has produced Ruppy, the first dog carrying artificial DNA – in this case for red fluorescent protein.

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Ruppy with nose, paws claws colored red

By now the cloning of dogs has become commercially available. In 2009 a couple from Florida had their dead dog cloned by a South Korean biotech company for 150.000$.