John Hammond - Sea lion cancers

Kat - In the 1980s, Frances Gulland and her team at the Marine Mammal Center in Sausalito on the California coast noticed an increasing number of wild sealions getting stranded or washing up dead on the beaches with urogenital cancers. In fact, these cancers are a major cause of death in the sealion population. Because it's unusual for wild animals to be affected by cancer to this extent, Dr John Hammond at the BBSRC Pirbright Institute in Surrey wanted to find out more about what might be causing them, and if there was a genetic link.

John -   Several people before I was involved in this have found that it's quite a complex cancer in that, like a lot of cancers, there are a lot of factors that are going to causing this cancer in an individual.  So, it's not an obvious association with one particular gene or one particular environmental variable.  A colleague of mine, she was doing some population genetics with the California sealions and she was looking at inbreeding in the populations around California and the west coast of the states and if there's any association with infectious diseases.  What she found is there's one particular microsatellite locus that seems to be associated with this cancer.

Kat -   So this means, the animals that have this type of cancer, they have this particular genetic variation in their DNA.

John -   Or a significant number did.  So, these microsatellites are hypervariable regions.  They're not necessarily functional.  They're just markers in an animal's genome.  They've been used over many years now in many, many different species to look at the population structures because these are regions that differ subtly between individuals within a population.

Kat -   How did you home in on a gene that might be involved in these cancers?

John -   We took that region and Elsa Hall and her colleagues at the Sea Mammal Research Centre, they did a very neat case control study involving quite an impressive number of animals, considering that this is a wildlife species.  They found that there was a significant association of homozygosity at this one microsatellite marker and prevalence of the carcinoma.

Kat -   That means that this marker is on both of the chromosomes - the one they've got from mum and the one they've got from dad.

John -   Yes, so if both copies of your genome have the same microsatellite sequence then there was an association that you were more likely to get cancer than if you had two different versions of this microsatellite.  So, it's just used as a marker.

Kat -   So homing in then, what do we know about what might be going on then at a genetic level that's causing these animals to become sick?

John -   There is no genome for a sealion as yet and so, the nearest genome that we had was, or we still have is the dog, which separated from the sea or sealion lineage about 45 million years ago.  So quite a while, but nevertheless, they're still carnivores.  They're all carnivores.  We sequence this very short region and I was able to use some comparative genomic work and find a region of the extended microsatellite sequence that had significant identity within the dog genome.

Kat -   So, it's basically a match between the region in sealions and the region in dogs.

John -   Yes.  Once I had a region in the dog genome, I was able to then extend the region that we assumed that the microsatellite was in in the sealion, get some more sequence data from the dog and then go in and look in more detail at the sealion.  So, when we compared it with other mammalian species we found that its region of the genome is conserved across mammals.

Kat -   So, what's lurking in there?  Have you got any good suspects?

John -   So, the region is actually within a gene called Heparanase 2.  Heparanase 2 is actually quite an understudied gene, but it has been implicated in many cancers particularly in humans.  It's obviously a very neat association that we find that a microsatellite associated with carcinoma in sealions happens to lie within what would be considered a good candidate gene to be involved in that process.  We haven't established a direct link but it is intriguing.

Kat -   So, what next for this?  I mean obviously, it's very sad for the sealions that they're being affected by this cancer.  But how is this information going to potentially help them in the future?

John -   Clearly, a lot of animals are suffering from this disease and at some point, it is untreatable and the animals has to be euthanized.  As I said earlier, it's actually a very complex cancer.  So, it's not just the genetics that are involved in being more susceptible or less susceptible to this cancer.  There are lots of other things that have been implicated including environmental contaminants, which I think are important, potentially some other genetic markers and also herpes viral infection.  So, when it comes to helping the sealions, if we can begin to establish how these factors interplay with each other, we might be able to reduce the prevalence of this cancer.  And also, it will help in the treatment of the animals if we can understand from their genotype, how likely they are to develop cancer or recover from cancer, or be treatable, then that also helps in the management of the population.

Kat - That was John Hammond, from the Pirbright Institute. And his research was published in the Proceedings of the Royal Society B journal last month - the reference is on our website, that's Nakedscientists.com/genetics