Training the dog in front of me

It's been hard to train two dogs at once. My old dog, Jack, never minded when I trained my young dog, Jenny. He was happy to chill out on the couch. But Jenny is different now that she's the old dog and Dash is the young dog: she wants to be part of whatever I'm doing, especially if it involves food. If I baby-gate her in another room while I train the puppy (and puppies take a lot of training) then she will sit right up against the gate and obsess. (Up side: gates have become much less scary to her recently, even though they are just as likely as they always were to fall down and go boom.) When I try to put her upstairs, she goes reluctantly and is ramped up and anxious when I let her out.

I read "A Secret to Training Two Dogs" by Eileen And Dogs, and determined that I would use mat training. I'd been told time and again that I should be mat training Jenny anyways: take the mat to the scary new place, and you have a safe haven for your shy dog. (Jenny is still extremely shy, though hugely improved from when I got her.)

I got a Mutt Matt for Dash and pulled a tiny old area rug out of storage for Jenny. Dash picked up the mat concept quickly: you lie down on it and get treats. In fact I now have trouble prying him off of it to put it away.

Dash on his mat.

But Jenny couldn't seem to do it. She eventually learned to lie down on her mat, but didn't like to stay on it. I tried asking them both to stay on their mats while I walked around them: Dash was glued to his, but Jenny would come off of hers and wander away.

This morning I unrolled Dash's mat and asked him to go to it, and Jenny went and hopped on the couch. The light bulb went off: this is my dog who refused to touch foot to ground unless absolutely necessary for the first months I had her. She lived on couches. I had to train her to get off of them. I used target practice with a yogurt lid that I moved farther and farther from the couch; she came up with the solution of picking the lid up and putting it back on the couch so she could keep getting rewarded without having to leave her safe space. The first time I saw her sleeping on the floor, four years after coming to live with me, I almost cried from joy. She even already has a "go to your couch" command which is quite strong.

Jenny training on her couch, shortly after she came to live with me.

So I trained Dash while she was on her couch, and then trained her while Dash was on his mat, and it was lovely. Both dogs were stuck in place until I asked them to get off. I was able to train something fun (a tunnel) working one dog at a time (with frequent treats thrown to the other).

The moral, as Denise Fenzi tells us in her excellent blog post, is to Train the Dog in Front of You. See what works for her, not what you think should work for all dogs.

Which leaves me to figure out how I will take a couch with me to the next strange place I need to bring Jenny...

Jenny on her couch two years ago.

The Replacement Dog: how a veterinarian / dog rescuer / geneticist searched for the right puppy

The death of my fifteen year old golden retriever Jack wasn’t just about my loss. It was about finding someone else to do his job, which for the last five years had been serving as a security blanket for Jenny, my shy collie mix. Jenny depended on him to tell her when people did not intend to eat her, to run interference with well-meaning strangers, and to demonstrate calm at the veterinary clinic. We could not remain a single dog household for long.

Jack and Jenny

I adopted Jenny at age 13 months. She had never been off the farm where she was born until her surrender to a shelter, and the world proved much larger than she expected. Jenny has excellent dog skills but a crippling anxiety upon encountering new people or environments. I adopted her knowing about her idiosyncrasies because I wanted to study anxiety in dogs, and wanted to experience it first hand. And so I have; living with Jenny has informed my understanding of anxiety in a way that reading about it never could have.

In my research, studying the way genetics and environment interact to affect the risk of anxiety has brought me back time and again to the importance of early environment: in utero environment, early maternal care, and puppy socialization. How the brain changes during and after the socialization period turns out to be a huge part of my research interests, and to learn from the source as I had done with Jenny, I would need a puppy, and a very young one at that. I’ve only adopted adult dogs in the past, but now is an excellent time for me to raise a puppy, as I work from home many days.

A puppy who would grow up to fit in well with Jenny had to fit a specific mold: confident around people and other dogs, but not so pushy as to annoy her. Someone she could play with. Someone male, because I didn’t want to deal with girl dog politics for the next ten years.

Jenny

Now, I have counseled others that adopting a very young mixed breed puppy from a shelter or rescue group means you really have no idea at all who you have just brought home, and that there is no shame in purchasing a dog from a responsible breeder. However, in practice, I balked at purchasing a dog. I completed an intense shelter medicine internship at the University of Florida several years ago, and I still feel part of that community. As the distance between the present day and that experience increases, I find myself holding tighter to those connections and looking for new ways to remain a part of sheltering. Purchasing a dog who was not going to be in want of a home felt a bit like eating humanely raised meat: I tell myself it’s okay for others to do it, but when I actually try to do it myself, some part of me rebels.

Yet as I looked at puppies from local rescue groups, in short order I found myself in a panic: could I really adopt a puppy whose genetics were completely unknown, whose parents I most likely couldn’t meet, and who had almost certainly had some early life trauma before ending up in foster care? Genetics and early experience are both critical in shaping the adult personality, and while I hope I could handle dealing with another shy dog, Jenny needed someone dependable, not another neurotic failing to keep it together when the mailman drove past.

When I started to seriously consider purchasing a dog, I had to decide on a breed. I love retriever-collie mixes: ideally the best of both worlds, retriever-social and collie-smart. But finding a responsible breeder of retriever-collie mixes seemed a tall order. Border collies are too intense for me. Australian shepherds have their tails docked so short. And I wanted to find a breed that is not recognized by the AKC, that is absolutely not bred for looks, that possibly even has open stud books to keep the genetics pool large and diverse.

I found the Scotch Collie and the English Shepherd. The Scotch Collie club had an open stud book policy going for it (good for them!). The English Shepherd club had a closed stud book policy (open it up, guys!) but it had been open relatively recently, the breed isn’t recognized by the AKC, and the dogs can’t be shown in conformation classes. The breed is a versatile working breed. Both breeds have lovely breed standards that accept a wide range of phenotypes (for example, 30-80 lbs in adult weight - a wide range!), which in itself tells the story of breeding for temperament and not looks.

In the end, I chose the English Shepherd based on the fact that there are more of them around, so it was easier to find a litter promptly. Waiting a few months would mean potty training a puppy in January in the Midwest, an experience I’ll leave to others.

The English Shepherd club maintained a list of breeders who had available puppies, with lots of information about the parents. It’s a well designed resource, and I link to it not to encourage others to run out and get an ES puppy (they are smart and high energy and not for everyone) but to provide an example of what kinds of information should be provided about available litters.

I screened the descriptions of parents: I discarded those who weighed more than 70 lbs, as managing Jack in his dotage had been hard on my back. I discarded those who were described as “protective” or “taking some time to warm up to people.” I checked that the parents had passed the relevant genetic tests (for this breed, tests for several eye diseases and hip dysplasia). Then I looked at the remaining breeders’ websites.

The breeders I liked talked about how they raised the puppies: giving them lots of positive experiences. They talked about what they did with the puppies’ parents - agility, nosework, herding. They often had long applications for potential owners to fill out, which asked all the questions they should: How will you exercise this dog? Do you have a fenced yard? What will you do if he is destructive?

I found a litter in Virginia with a male who sounded perfect: confident, social, and by the way athletic. My husband and I stuffed Jenny into the car and drove 9.5 hours to pick up our boy. He cost, by the way, probably more than twice what a rescue puppy would have cost, but I have paid for knowing that he is clear of some genetic diseases for which he might have been at risk, and for knowing that he was in the uterus of a calm, happy mother; raised with a litter who had plenty of high quality food and safe places; and had extensive early socialization (including the Early Neurological Stimulation and Early Scent Stimulation programs). He has proven, in his first week and a half with us, to be social and sweet, willing to settle down when asked so long as he is given plenty of exercise and mental stimulation, and terrifyingly smart. He and Jenny are already wrestling for hours daily, laying the foundation for what I trust will be a long friendship.

That is the story of how we found Dashiell.

Dashiell

Corrigendum on a recent tame fox article

I came across a new article on the Russian tame foxes today, Russian geneticist repeats dog domestication with foxes in just fifty years. It's a nice summary of the Farm Fox Experiment, although I’m not sure why I've seen two stories covering the tame foxes this week — there’s nothing new going on with them! Why two stories in such a short time period?
 

This article does have a few mistakes in it:

 

[Belyaev] and his intern, Lyudmila Trut, wandered around Russia searching for foxes to start their experiment. Foxes were chosen based on their behavior in the presence of humans. Those that showed slightly more tolerance of humans were brought back to their Novosibirsk lab to serve as the start group.

and his intern, Lyudmila Trut, wandered around Russia searching for foxes to start their experiment. Foxes were chosen based on their behavior in the presence of humans. Those that showed slightly more tolerance of humans were brought back to their Novosibirsk lab to serve as the start group.

Read more at: http://phys.org/news/2016-09-russian-geneticist-dog-domestication-foxes.html#jCp

and his intern, Lyudmila Trut, wandered around Russia searching for foxes to start their experiment. Foxes were chosen based on their behavior in the presence of humans. Those that showed slightly more tolerance of humans were brought back to their Novosibirsk lab to serve as the start group.

Read more at: http://phys.org/news/2016-09-russian-geneticist-dog-domestication-foxes.html#j

and his intern, Lyudmila Trut, wandered around Russia searching for foxes to start their experiment. Foxes were chosen based on their behavior in the presence of humans. Those that showed slightly more tolerance of humans were brought back to their Novosibirsk lab to serve as the start group.

Read more at: http://phys.org/news/2016-09-russian-geneticist-dog-domestication-foxes.html#jCp

 

 The original foxes were imported from Canadian fox farms, not chosen from around Russia as this article says. Also, the very first foxes selected for the founding population of the study were not chosen based on their behavior. A control group was kept, so the researchers (of which there are more than two) didn’t want that first set to be more friendly than the average farm fox.

 

[The changes were] not all on the outside—their adrenal glands became more active, resulting in higher levels of serotonin in their brains, which is known to mute aggressive behavior.

 

The tame foxes’ adrenal glands became less active, and secreted less cortisol, a hormone which is associated with stress. Additionally, they have been shown to have higher levels of serotonin in their brains (not secreted by their adrenals, however), which is associated with less aggressive behavior, though I think saying that serotonin “mutes” aggressive behavior might be going a bit far. We don’t fully understand the link between serotonin and aggression.

I do like seeing the Farm Fox Experiment covered in the popular press, though. It’s such a great way of explaining how selection works and such a fascinating demonstration of how quickly selection can have an effect!

And it was not all on the outside—their adrenal glands became more active, resulting in higher levels of serotonin in their brains, which is known to mute aggressive behavior.

Read more at: http://phys.org/news/2016-09-russian-geneticist-dog-domestication-foxes.html#jCpMore importantly, the adrenals don’t control serotonin levels in the brain. They release cortisol into the blood stream. Tame foxes show reduced levels of both cortisol and serotonin compared to control foxes, but those are two different things.

 

Where did dogs come from?

What we know and what we don’t know about dog domestication

Want to learn more about dog domestication? It's not too late to sign up for my online class, From Domestication to Inbreeding!

Dogs evolved from wolves. We’ve been certain of that for several decades by now. But there remain a lot of questions: exactly when did dogs first appear? Did they join their fate with humans when we were hunter-gatherers, or were they attracted to us after the Agricultural Revolution, because we had begun to farm? Which group of ancient wolves did they come from? Knowing more about where dogs began will help us understand modern dogs and their behavior better. Academics are currently conducting a very polite debate about these questions in journals, waged over the course of years.

Grey Wolf

Why is the problem such a hard one? Until recently, the tools that we were using to get information about ancient canids were very limited. Our first tool was archaeology: digging up the remains of ancient canids, trying to figure out if the animal was more dog-like or more wolf-like, and then estimating the age of the find. It’s not entirely straightforward to tell an ancient dog from an ancient wolf using only bones, especially when many archaeological finds are incomplete. The important parts of the skeleton for this work are the teeth and skull: dog muzzles are shorter than wolf muzzles, so that their teeth are more crowded into the available space, and the last premolar and first molar are smaller in dogs than in wolves. Some interesting finds have suggested that dog-like canids first appeared between 15,000-30,0000 years ago — that’s just before agriculture was first developed.

A well publicized 1997 paper from Vilà et al. popularized a new tool for dating dog domestication: analysis of mitochondrial DNA, or mtDNA. Mitochondrial DNA is the DNA inside the mitochochondria in our cells. Mitochondria used to be free-living organisms; they began to live symbiotically in the cells of multi-cellular organisms billions of years ago, but still have their own separate DNA. Mitochondrial DNA gains new mutations at a regular rate, and this can be used as a molecular clock: compare the mtDNA of two different species, and by counting the differences, you can estimate how many years ago the ancestral species split into the two new species.

The problem is that this molecular clock isn’t very reliable or very precise: we don’t really know exactly how fast mtDNA mutates, which makes the clock hard to calibrate. The 1997 findings suggested that dogs and wolves separated about 130,000 years ago — an order of magnitude more than the archaeological estimates suggested! Other mtDNA studies have been conducted since then, with a variety of results, none of them conclusive. It turns out that dog and wolf mtDNA divergence is particularly difficult to analyze because dogs and wolves can and do still interbreed. My golden retriever may not have a wolf in his immediate ancestry, but I suspect you don’t have to go back all that many thousands of years to find one — certainly not all the way back to the domestication split. And there are quite a few populations of dogs in the world with much more recent wolf ancestry than that. This interbreeding really screws up the molecular clock.

In the last few years, though, the revolution in genomic tools — cheap and efficient sequencing of complete genomes — has gotten to the point where it’s affordable to completely sequence the genomes of a number of dogs and wolves for a study. This is significantly changing the kinds of things we can learn about how dogs and wolves genetically differ. Instead of guessing at changes in mtDNA, we can look at the actual genes that differ between the two species. These new studies have set the date of dog domestication at 11,000-32,000 years ago, a date which is similar enough to the archaeological findings to make a lot of sense.

We’ve learned a lot of interesting things from these new sequencing studies beyond just a more precise date of domestication. A little more than a year ago, Axelsson et al. found that dogs make more of an enzyme for digesting starch than wolves do. The enzyme is called amylase, and dogs have multiple copies of the gene, whereas wolves have only one. These researchers wondered if this improved ability to digest starch meant that dogs were domesticated after the appearance of agriculture — if starch digestion was part of the domestication process. However, a study published in January 2014 by Freedman et al. dug deeper into the amylase question and discovered that in fact, not all dogs have extra amylase genes. Some ancient breeds, like the husky, do not. Neither does the dingo. These very recent findings suggest that dogs were in fact domesticated before the Agricultural Revolution, and that some breeds later developed an improved ability to eat what we eat, adapting to their new post-domestication diet. You might imagine that such a change would have been less important to the husky, living in the cold north as it did, where meat was on offer much more often than plants.

Freedman et al. also suggested that dogs didn’t actually evolve from wolves. Wait, what? It's possible that both dogs and wolves evolved from a different ancient canid which doesn’t exist any more. Freedman came to this conclusion using a somewhat complicated genomic analysis which doesn’t tell us anything about what such a canid would have been like, but it’s an idea which resonates with reservations I’ve always had about the “dogs came from wolves” theory. Wolves are so shy, so hesitant to come near humans, and so focused on making their living by hunting. The ancestors of dogs seem more likely to have been scavengers, willing to live close to humans. Maybe some ancient canid did give rise to both species — the one moving closer to human civilization and becoming dogs, the other farther away and becoming wolves. With several studies coming out every year about dog domestication, we may learn more very soon.

For more information, check out “How Much Is That in Dog Years? The Adventof Canine Population Genomics,”a recent open-access review article that provided much of the information in this story.

Note: this story was originally published in the summer 2014 issue of  The APDT Chronicle of the Dog.

Image by Isster17 (Own work) [CC BY-SA 4.0 (http://creativecommons.org/licenses/by-sa/4.0)], via Wikimedia Commons

References

Axelsson, Erik, et al. “The genomic signature of dog domestication reveals adaptation to a starch-rich diet.” Nature 495.7441 (2013): 360-364.

Freedman, Adam H., et al. “Genome sequencing highlights the dynamic early history of dogs.” PLoS genetics 10.1 (2014): e1004016.

Larson, Greger, and Daniel G. Bradley. “How Much Is That in Dog Years? The Advent of Canine Population Genomics.” PLoS genetics 10.1 (2014): e1004093.

Vilà, Carles, et al. “Multiple and ancient origins of the domestic dog.” Science 276.5319 (1997): 1687-1689.

Ruminations of a dog scientist on a 96-well plate

I've been doing a lot of bench work in the laboratory lately. This involves filling the tiny little wells on a plate with my ingredients (sample, reagents, primers) and then inserting the plate into a reader. The machine takes the plate up with whirring sounds that always fascinate me. I know there are little robot arms in there moving the plate into place, and I wish I could watch the process. But as I listen to the robot work, I sometimes think: is this the closest I get to living, moving animals now? How did I get here, so separated from fur and behaviors and emotions?

96 well PCR plate

My long term research goal is to understand the differences in how brains work in dogs who suffer from fear issues compared to resilient dogs who take life's arrows a bit more in stride. I'm doing this by studying gene expression in the brains of foxes who have been bred to be fearless (“tame”) or fearful (and aggressive — those who study them just refer to this line as “aggressive,” though).

My approach is, at the moment at least, deeply reductionist: what are the differences in gene expression in a few brain regions in these two lines of foxes? In other words, does one group make more of a certain kind of gene than the other? My hope is that I’ll be able to make some conclusions about the differences in function in these brain regions between the two lines of foxes, and that what I find will be relevant to fearful dogs. But I find myself burrowing deeper and deeper into learning about very small parts of the brain, and then very specific functions of those parts to the exclusion of other parts. Currently I’m learning about the pituitary gland — no, wait, just a particular cell type in the pituitary gland, the corticotroph — no, wait, just a particular set of processes of the corticotroph, how it releases one particular hormone into the bloodstream.

So in my daily work, I do things like take some tissue and extract all the RNA from it (throwing out DNA, proteins, cell structure, all sorts of interesting information — that's not what I'm working on or able to assess at the moment). I use PCR to extract a tiny piece of RNA from the complete transcriptome (all the RNA from that tissue), throwing out even more information. And then assess the expression level of that RNA, resulting in just one number. One number out of all that information after a day’s work.

Behavior can’t really be fully understood using this reductionist approach. If I do find a few important gene expression differences in a few small brain regions, they won’t explain the whole story of why an animal has a fearful personality. They’ll be a tiny, tiny piece of a complicated network of interactions involving genetics and life experience. But in order to get at that tapestry we have to first be able to visualize the threads that make it up. So here I am, in the trenches, doing that.

A recovering shy dog.

Geek version of the fat mutant labs FAQ

In the face of overwhelming demand (three people thought it sounded like a good idea), here is the geek version of the fat mutant labs FAQ, the nitty gritty about the study findings.

What gene is mutated and what does it do?

The gene itself is one of these weird ones that actually codes for multiple proteins. (Basic genetics usually assumes that one gene codes for one protein, of which there may be a few different but similar versions.) The gene in this study is POMC, or proopiomelanocortin. The “pro” means that it codes for a protein which doesn't itself do anything until it gets cut up some more. The rest of the long name describes the things it gets cut into:

• opio: short for opioid. Opiods are potent pain relievers; the classic opioid is morphine. If you or your pet has had surgery, you’ve probably used an opioid for pain relief during or after it. (There is currently a big scandal about drug companies and opioids in the news.) In this case, two of the products snipped out of POMC are endogenous (made by the body) opiods, β-endorphin and enkephalin. They are feel-good substances.
• melano: refers to melanocyte stimulating hormone (MSH). MSH has a bunch of different effects in different tissues, but most importantly has been associated in humans with effects in “controlling appetite,” our authors tell us.
• cortin: the coolest thing this gene makes is ACTH, which is released into the bloodstream to tell the adrenals (down by the kidneys) to release the “stress hormone,” cortisol. This is the system I study! But it is, it turns out, not really relevant to this particular study.

What was the mutation?

It was a 14 base pair deletion. The gene itself is thousands of base pairs long; in the dogs with the obesity-associated allele, they were missing just 14 base pairs. But remember, DNA bases (nucleotides) are translated into proteins in sets of 3. (Three nucleotides codes for one amino acid; a string of amino acids makes up a protein.) If you remove a chunk of bases that is not a number divisible by 3, suddenly the translation machinery that reads the DNA and produces proteins gets completely off track. It is just reading in sets of three. Now it’s off by one or two and suddenly it's creating entirely different amino acids, so the resulting protein is completely different after this point. This is called a “missense” mutation, because a protein is still generated, it's just made with different amino acids.

For example, the sentence “mad man sat” becomes gibberish if you mess up the spaces and make  “adm ans at” after removing just one letter.

So that’s what happened here: the first chunk of the POMC protein in these dogs with this allele is fine, but the second chunk is gibberish from the body’s point of view. Since the POMC protein gets cut up into smaller proteins with actual functions, this means that some of its products were fine, and some were not. The article has a lovely illustration of the situation, highlighting in red the products that are affected by the mutation.

Image from Raffan et al., 2016

The products that are broken in dogs with this allele are β-MSH and β-endorphin. The first, you will remember, has been associated with control of appetite in humans. (And it’s apparently somewhat different in rodents, so it’s hard to test its function in laboratory mice, so it was exciting to find it in dogs so we can learn more about obesity!) The second is one of the endogenous opioids, a feel good substance.

How do these broken proteins cause obesity?

We don’t know. The authors write:

The mechanism by which reduced β-MSH and β-endorphin due to the mutation causes behavioral and weight phenotypes remains to be precisely elucidated...  However, studies of humans with POMC mutations resulting in aberrant forms of β-MSH ... have suggested that β-MSH is important in controlling appetite and obesity development in man, with hyperphagia notable in patients with both mutations... The role of β-endorphin in regulating appetite, satiety, and energy balance is less well understood, but it has been proposed to underlie oro-sensory reward in high-need states or when the stimulus is especially valuable. However, mice selectively lacking β-endorphin are hyperphagic and obese, suggesting that the loss of both neuropeptides could contribute, in combination, to the phenotype seen in dogs carrying this frameshift POMC mutation.

 So, we don’t know, but we know MSH problems make people more likely to eat a lot, and β-endorphin may have to do with the feeling of reward after eating.

How did they find the gene?

They guessed! They had a small number of genes that they thought might have to do with obesity, and they checked them out in some labs. They looked for different versions of the genes in different dogs, and then looked for alleles (versions) which were more common in fat labs than not fat labs. They found one hit — this particular allele of POMC.

This is known as a “candidate gene” approach: when you pick a gene that you think might have an effect in a particular phenotype and test it out specifically. It has historically been less productive than “hypothesis free” approaches in which you basically ask about all the genes you possibly can if they have something to do with the phenotype. This is because our guesses about which genes affect which phenotypes turn out to be wrong so often. So these authors got lucky to get a result!

Was their sample size big enough?

I hadn’t considered getting into the statistics (I hate statistics) but some people actually asked about them. Yeah, I like their numbers for a candidate gene approach. To get reliable results using some other methods they would have needed more dogs, but when you’re just asking questions about a few genes, it’s fine to have a smaller number (in this case, 310).

I’d be more concerned about where their dogs came from. They tell us:

Labrador retriever samples were collected from dogs from a large assistance dog breeding colony (n = 81) or that were pet dogs from the UK (n = 310). Pet dogs were recruited either after their owners volunteered in response to an email from the UK Kennel Club sent to over 15,000 Labrador retriever owners, or via participating veterinary practices.

This sounds reasonable enough. But if I wanted to play devil’s advocate, I’d suggest that they were biasing themselves to a particular kind of owner, the kind of owner who responds to UK Kennel Club email. These owners may be more likely to breed and/or show labs, and therefore these labs may have a slightly different genetic background than some other group of labs. For example, perhaps some famous show lab sire who sired thousands of puppies happened to have this mutation. And then perhaps labs that are shown are more likely to be fat than labs who are not (because UK judges actually reward obesity in show labs — don’t get me started on that). If that happened, it would throw off the statistics and you might see a spurious correlation between the mutation and obesity.

That’s just me spinning tales. I think their methods are pretty standard; it’s hard to recruit pet dogs to these kinds of studies and they did it the usual way. It's quite interesting that they found a mutation which is so clear in its loss of function of the protein. If the correlation is indeed spurious, subsequent studies using different populations of labs should show us.

Any more questions?

What else do you guys want to know? I tend to focus on stuff in studies that I find interesting. What do you find interesting?

Learn more genetics

As before, I will shamelessly take the opportunity to plug my upcoming genetics class. It is not too late to sign up; it starts Monday, May 9, but you can sign up several days late.

Raffan, Eleanor, et al. "A Deletion in the Canine POMC Gene Is Associated with Weight and Appetite in Obesity-Prone Labrador Retriever Dogs." Cell Metabolism (2016).

Fat mutant labradors FAQ

The study about a mutation associated with obesity in labrador retrievers has received massive news coverage for a dog genetics article (and you can see how happy the researchers are about it at @GODogsProject). So what does it mean for your dog?

Image: Raffan et al., 2016

• Do all labs have this mutation? No. They tested 383 UK labs and found that of 383 Labrador retrievers from the UK, 78% of them didn't have this mutation at all; 20% had one copy of the mutation (were heterozygous); and 2% had two copies (the maximum number you can have; they were homozygous). They tested some US labs as well and found similar frequencies.
• Do any other breeds have this mutation? Yes, it was also found in flat-coated retrievers, a breed closely related to the lab. The researchers tested 38 other breeds, testing 8-55 dogs per breed. (The list of breeds they tested is provided.) They tested 55 golden retrievers, another closely related breed to the lab, without finding this mutation. That doesn’t mean it’s not out there, but it does suggest that if it is present in other breeds, it’s much less common in them than in labs.
• If my dog has this mutation, does it mean my dog is doomed to be fat? No. They did show an association between the mutation and weight: dogs who have one copy of the mutation are, on average, 1.90 kg (4.18 lbs) heavier than dogs who have no copies. Dogs who have two copies are on average 3.8 kg heavier than dogs who have no copies. (This is in labs, but the numbers in flatties are very similar.) But that’s an average. It’s not all about genetics. Some dogs who have this mutation won’t put on that much extra weight, and some dogs who have it will put on more. The gene they studied will interact with other genes to affect your dog’s eating habits and metabolism, and of course in weight gain as in behavior, the environment (food type, food amount, exercise) is a huge factor.
• If my dog is fat, does it mean my dog probably has this mutation? Not necessarily. There are lots of reasons to get fat.
• Is this “the gene” for weight gain? In dogs as in humans, multiple genes control weight. This is just one, albeit one with a pretty impressive effect in this breed. And again, remember the importance of environmental factors!
• How does this mutation cause weight gain? It may have to do with causing dogs to want to eat more (certainly a trait we’ve all seen in labs!). It may also change their metabolism directly, affecting how they turn calories into energy.
• Where did the mutation come from? Both labs and flat-coats are descended from the St. John’s water dog, a breed which is no longer around. The researchers have reason to believe that the mutation dates back to that breed.
• Does this mutation make labs easier to train? Possibly. The researchers tested a population of labs who are used as breeding stock for assistance dogs, and found that many more of them carried the mutation than in the general population: 23% had zero copies, 64% had one copy, and 12% had two copies. Additional genetic analysis suggested that these dogs are being actively selected for this mutation (unbeknownst to the people who are selecting them!). This suggests that something about this mutation makes dogs better at assistance work — perhaps making them more food motivated and easier to train.
• Does this mutation make flat-coats fat, too? It does, and yet flatties aren’t known for obesity the way labs are. It’s a bit of a head scratcher.
• What's the big deal? Didn’t we already know that labs are food-obsessed mutants? I know, right?

Raffan, Eleanor, et al. "A Deletion in the Canine POMC Gene Is Associated with Weight and Appetite in Obesity-Prone Labrador Retriever Dogs." Cell Metabolism (2016). It’s open access and, as modern genetics papers go, not that hard a read. Check it out!

Want to know more about dogs and genetics? I have a class on it starting Monday, May 9! We will learn concepts like homozygosity and heterozygosity, and I will be happy to discuss this study in more depth.

Dogs and hugs FAQ

Stanley Coren, well known and respected author on dog cognition, recently published a blog post about dogs not enjoying hugs. Now that I have been asked to weigh in on his post by my father ("that can't be true!"), my lab mate ("Jessica will have some useful insights about this!"), and multiple dog park friends, I feel compelled to spread my wisdom across the internet for the benefit of all, whether they want it or not.

Source: The Data Says "Don't Hug the Dog!", Stanley Coren, Psychology Today

1. Does your dog enjoy being petted by you? Almost certainly.
2. Does your dog enjoy being grabbed and squeezed? Probably not.
3. Do any dogs enjoy being grabbed and squeezed? I am sure there are some. I know some dogs who enjoy all interactions with humans up to and including getting whacked up side the head (I live with one). But as a species generalization, I believe they mostly don't.
4. Should you hug random dogs when you meet them? Absolutely not. But you knew that already, right?
5. Should you hug your own dog? Sure. I do it to my dogs sometimes. Just be aware that you are doing it for your own enjoyment, not theirs. My dogs tolerate the occasional squoze. I tolerate being punched in the butt when I get home from work.
6. How can it be that dogs, who love us so much, don't enjoy hugs, which we enjoy so much? Well, note that primates really love pressing our tummies against each other, but canids don't (except when they are initiating sex or displaying poor manners). They display affection other ways: licking you in the face, sitting next to you, leaning on you. With someone who moves at the same pace they do, you sometimes see them walking or running shoulder to shoulder. I would love to hear from people about what they think their dogs do instead of hugging.
7. Was Coren's study a good study? It wasn't actually a study, and Coren didn't say it was; in his blog post, he refers to it as data. This data set was pretty interesting and it was nice of him to share it with us. It would be even nicer if someone did a study using similar approaches, but with a control group, maybe having the person scoring the dog body language blinded to the group the dog is in (editing out the human so you can't see the hug?), and published it in a peer reviewed journal. Oh, and while I'm asking, make it an open access journal, please.
8. Where can I learn more about dogs and hugs? In my mind the best resource is Dr. Patricia McConnell's coverage in her classic book, The Other End of the Leash. Which is a must-read for oh so many reasons.

From the genetics of dog breeds to stress and reproduction

The other morning I was talking to my husband in bed in an attempt to help him wake up.

Me: So I ran into our friend who walks those three goldens separately yesterday and we had a nice conversation. She said she’d read my blog and had a dog genetics question for me.

Him: mmmppphh

Me: She said she’d heard that 1% of dog genes account for all the differences between breeds and asked me if it was true. I pointed out that 1% of 20,000 is still a lot of genes, and also explained that it's really hard to use statistics like that to describe genomic differences, because you can measure those differences in so many different ways.

Him: Did you tell her that humans and chips are 98% similar genetically?

Me: Yes I did.

Him: But I’ve been seeing that for at least 10, maybe 20 years. Is it still true?

I consulted the internet on my phone.

Me: Let's see... The Smithsonian Institute says we're 1.2% different from them. I think I'll skip this link to the Institute for Creation Research -- is that really the second hit on “human chimp genetic similarity”?! Ah, Wikipedia gives more information: “The alignable sequences within genomes of humans and chimpanzees differ by about 35 million single-nucleotide substitutions. Additionally about 3% of the complete genomes differ by deletions, insertions and duplications. Since mutation rate is relatively constant, roughly one half of these changes occurred in the human lineage.” Well, that’s not true.

Him: What?

Me: Mutation rate isn’t constant.

Him: It’s not?

Me: Well it is closer to constant in specific areas, like parts of the mitochondrial DNA, which we like to use as clocks. But over the whole genome, which is what they're talking about here, no. Different areas evolve at different rates. There are hotspots that go faster. And then the whole species might change faster when its environment suddenly changes. Like if you're in a lovely sunny valley and you're well adapted to it and then suddenly an Ice Age starts and your valley fills with ice and you suddenly have intense selection pressure to change your coat length and thickness and your diet and things like that. The stress itself can change your mutation rate.

Him: Stress can’t change your mutation rate! How would that even work? If a female is stressed, it’s too late, her eggs are already made.

Me: Her grandkids then? Or only sperm have more mutations? Hmm, that’s good point.

I consult the internet again. I find and discard an article about yeast evolving more quickly under stressful conditions. Yeast don't make eggs or sperm as part of their reproductive process.

Me: Here you go. Flies. Close enough to mammals for you? Stress does cause flies to have offspring with more mutations. It makes sense because if you’re stressed, it means you're probably not well adapted to your environment, so you should do the random shuffle with your kids’ genetics in the hopes that something, anything, different will give them a better shot. Mostly they’ll be worse off, but at that point it’s worth if it a few are better off and can pass on those genes.

Him: But how does it work with female flies having already made their eggs before they’re stressed?

Me: I dunno... Hang on... Here we are. OK, so the researchers mutated the males, their sperm.

The reason the researchers mutated the males has to do with how DNA is fixed in male and female fruit flies. There is almost no DNA repair in sperm. But the egg can repair DNA in any sperm that fertilizes it.

So the researchers were basically asking how much of the mutated DNA from the male could slip through the repair processes in the egg. The answer was that eggs from stressed females let a lot more mutations through.

Why would stressed female eggs not fix DNA as well? Probably because fixing DNA perfectly costs lots of energy. And these stressed females may not have had enough energy to spare.

There are two different kinds of DNA repair out there. The one that fixes the DNA perfectly costs a lot of energy. The other kind gets rid of any gross problems but leaves errors behind. This costs less energy but leads to more mutations.

The idea is that stressed females can't afford to use the perfect DNA repair system. So they use the other one. Their kids survive but they have more mutations.

—Stanford at the Tech, Understanding Genetics

 Me: Oh crap now I’m late to take Jack to physical therapy.

...Kind of makes you wonder about puppies conceived in puppy mills or animals conceived in hoarding situations, doesn’t it? Might they have more mutations than animals conceived in less stressful environments?

Science liveblogging: vasopressin in the stress response

Why are puppy vaccination schedules so crazy?

Next week I'm giving on a webinar about puppy vaccine schedules. I'm aiming the webinar at people who have to explain to puppy owners why the crazy schedule, why they can't go to the dog park even though they have all the vaccines they need at this point, why they should socialize but be cautious... We will start with a whirlwind tour of the immune system to give you guys a good grounding to understand why puppy vaccines have to be given every 3-4 weeks. There will be scary parvo stories and photos of cute puppies and cute immune cells and fun biology facts and suggestions on what to do about that vet who thinks socialization isn't all that important. It will be a blast, you should come and ask me lots of questions!

When: Wednesday, March 23, 8-9pm ET
Where: sign up with the Pet Professional Guild
CEUs: Yes, 1!

Questions about whether this webinar will be helpful for you? Ask me here or on Twitter (@dogzombieblog).

Being the one who remembers: humane housing in shelters

A cat who is clearly not in a shelter.

Last night I wrote the first draft of a document on appropriate housing for shelter animals for IAABC’s new shelter division. Before getting into the nitty gritty details, I wrote as part of the general overview:

Housing for any shelter animal should be clean and safe: easy to sanitize; no sharp edges that could injure the animal; no gaps or broken latches that could allow the animal to escape. Animals should not be housed in temporary enclosures like airplane crates for more than a few hours while longer term housing is located.

I wondered: Is this too basic to even cover? Will readers stop reading the document at this point, thinking it’s worthless?

But then I remembered the story of a cat I encountered at a shelter during my internship. I was working in the kitten house, a small house dedicated to raising kittens during The Season. The cages were mostly roomy enough for moms with their litters; smaller cages were reserved for litters of orphan kittens. But one small cage had an elderly adult cat in it.

This cage was just too small for this cat. Now, some shelters keep all their cats in cages like this. But the thing was, this was a really excellent shelter. They did a great job of providing their cats with roomy housing. And their vet knew the importance of good housing and advocated for it, and moreover had enough authority to make it happen (sadly, a bit of a rarity in many shelters). So what was going on here?

I asked. Turns out, the cat had been adopted by a staff member but had proven to have behavoral issues that made it difficult for her to live in a home. So she had come back to the shelter. She also had a disease or two which made her expensive to keep and difficult to adopt. But the shelter wasn’t willing to euthanize her, so they put her in a spare cage in the kitten house and planned to figure out the situation later. And hadn’t figured it out yet, because in a shelter, there’s always some more pressing problem that has to be figured out today.

What it took for this cat to get good housing was for someone to notice and make her a priority. We moved her into the bathroom for a few days so she could have more legroom, and she hung out with me in the guest bedroom at night. I found a roomy wire crate intended for litters of kittens and we set that up for her for her evenings long term, and during the days she got to hang out on the desk of the kitten house manager.

And that is often the job of the person at a shelter who works on animal behavior and welfare. Not training. Not making plans for Kong programs. Not fighting to change whole banks of cat cages out for something better. But noticing one single animal who got forgotten in an airline crate in a corner. Being the advocate for the little things. Being the one who remembers.

Dog parks: tools to be used for good or evil

Dog parks can be valuable ways to exercise and socialize your dog. They can also be dangerous places where dogs can get hurt. And so we ask ourselves: are dog parks a good thing or a bad thing? I argue that they are neither. Like retractable leashes, they are just a tool that can be used well or badly.

Park design

The design of a dog park can have a lot to do with how well it functions. I think the size of the park is incredibly important. At my local park, we have a lot of space. And I use this space with my dogs. If there is a group of dogs that my dogs aren’t getting along well with, and I see trouble brewing, I move on to a different part of the park. In a small park, this wouldn't be possible.

Jenny at my fabulous local park

My local park also has a smaller area, separately fenced. It’s a great place to take a smaller dog when the park is full of big dogs, or to take a dog who needs a cooling down period after he's been acting like a bully. I don’t use this space much with my dogs, but it’s extremely helpful for a friend of mine who’s trying to teach her six month old to restrain his enthusiasm around other dogs by giving him time outs when he fails to control himself appropriately.

Park timing

I don’t go to the park when it’s crowded. Of course, it’s crowded at the times that are the most convenient for the most people: late afternoon, weekends, when the weather is lovely. I go in the mornings during the week. I lead a lifestyle which makes that possible (though I have to push back at work to protect that time). If you can only go to the park when it’s crowded, it might not be worth going at all. Tempers run high when dogs are packed in together with no real room to get away.

Dog management

This is the important one for me: I am always alert and managing my dogs. I keep an eye on them. One of them can have a short temper with other dogs, and I keep her moving, away from groups. If I see her meeting another dog, I am watching closely for her to get tense, and if I don't think it's going well, I call her away before something goes wrong.

This kind of management is hard for a lot of owners who don’t understand dog body language well. For this reason, I’ve founded a group at my local park with the goal of (among other things) providing educational material at the park to help owners understand how to identify and avoid problems before they start. Not everyone will be interested in this material, and that’s why it’s also important to me to attend a large park during low occupancy times.

Stuff happens

My dogs have been attacked at the park. One of my dogs has also been attacked while I was walking him on leash on a sidewalk. And once he got away from me and was almost hit by a car. That’s life. Is it more dangerous at the park than on a leash on the sidewalk? Possibly, though I’d love to see evidence one way or the other. Is it more dangerous to a young dog to fail to get his crazies out on leash, and then be at risk of being surrendered by a frustrated owner? Again, I can’t say, but there are risks to any choices about how we manage our dogs.

At the park, there are no cars, no cats, no children, no bicycles, no terrifying joggers just begging to be bitten. One of my park friends walked her dog on leash until he bit a roller blader who passed too close. Without the park, she would be unable to exercise her dog safely. My shy dog Jenny has made canine and human friends at the park that she is unable to make in situations in which she's restrained. She has made incredible gains in confidence. That has come at a risk, but to me, with a lot of careful management of the dog park environment, at the right park, with these dogs, it’s worth it.

Too many pairs: DNA, chromatin, and chromosomes

Some facts:

• Molecules of DNA are double-stranded, each strand a perfect complementary copy of the other.
• Humans have 23 pairs of chromosomes.
• Chromosomes are made of DNA.
• We have two copies of each gene.

Where do these two copies of each gene come from — the complementary DNA? Or the pairs of chromosomes? In fact, what is the relationship between DNA and chromosomes? These questions have proven thorny for students in the past, so I'll try here to describe the two different ways in which genetic information is duplicated in a cell.

1. Complementary copies of DNA strands

Molecules of DNA duplicate the information they carry. Each base in a DNA strand is bonded to its complement on the opposite strand: A bonds to T, C bonds to G. It’s like a backup mechanism: if something happens to one part of the strand, the other half is there with the complement of the information. So that’s the first way in which genetic information is paired. And the important part about this pairing is that the pairs are exact complements of each other, like mirror images: the information is duplicated precisely and does not vary.

Part of a DNA strand, demonstrating complementary bases in matching colors

This double-stranded molecule of DNA, then, is wrapped up tightly around proteins called histones, and this set of spools of DNA and histones all together is a material called chromatin.

Chromatin: light blue/green strands of DNA wrapped around bright blue histones.

2. Two copies of each chromosome

Chromosomes are made out of chromatin. In a lot of the pictures of chromosomes in which you can see the chromatin that makes it up, the chromatin looks sort of like yarn woven into a sweater. That’s a reasonable way to think of chromosomes: big structures (big enough that we can see them with a not-too-powerful microscope) made from this yarn-like chromatin.

Cartoon of chromosome made of yarn-like chromatin. (Image by Magnus Manske at Wikipedia.)

 A particular gene is always on a particular chromosome in a given species. For example, the gene for oxytocin, OXT, is always on chromosome 24 in dogs and chromosome 20 in humans. So your chromosomes are very orderly, each one containing a specific set of genes.

Humans have 23 pairs of chromosomes. Dogs have 39 pairs. In fact, Wikipedia has a whole page devoted to the number of pairs of chromosomes in different species. We think of chromosomes as looking like big X. The X is actually the two separate chromosomes in a pair, stuck together during the process of cell division. Usually those two arms of the X are separate in the cell.

Image by JWSchmidt at Wikipedia

In a pair of chromosomes, one chromosome is made of chromatin from one (double) strand of DNA and proteins, which you got from your mother; and the other chromosome is made of chromatin from another (double) strand of DNA and proteins, which you got from your father. So you have, for example, two copies of chromosome 20, one from your mother and one from your father.

Human chromosomes: 23 pairs.

These pairs of chromosomes are the second way in which your genetic information is paired. But this is very different from the exact copy pairing of strands of DNA. Your version of the OXT gene on the chromosome you got from your mother may be slightly different from your version of the OXT gene on the chromosome you got from your father. Where her version had a G-C, his version may have an A-T. (Or it may be just the same.)

DNA differences on two different copies of the same chromosome (see the difference highlighted in blue).

So we have two versions of each gene, one on each chromosome in a matched pair. For a particular gene, we may have two identical copies (in which case we are “homozygous” for that gene) or we may have two different versions (in which case we are “heterozygous” for that gene).

So, yes, we essentially have four instances of each gene in each cell. That’s four instances, but a maximum of two versions of the gene (the doubled instances on a double strand of DNA are always identical complements; it’s only when you compare instances between chromosomes that you may see differences).

In the minds of geneticists, it’s the two versions in the pair of chromosomes which really count. That’s the pair that could differ, after all. And that’s why you'll hear that we have “two” copies of each gene, even though the gene is paired both in the DNA and again between chromosomes.

Science for the people

One of my students in the online genetics class I’m teaching commented to me that it was a little sad that we were marketing the class as “not too difficult.” Science is only as hard as you make it, she said. It shouldn’t be something scary.

It shouldn’t be, but for a lot of people it is. As a freshman in college I figured I should take college level biology as an elective so that I had a solid groundwork in how life works. (I was a medieval studies major.) But talking to my pre-med friends convinced me otherwise. Science classes were for people who were all in: they were only for scientists, not dabblers. They were hard work. Lots of hard work.

When I decided to go back to school to become a veterinarian, I took that introductory biology course, and a lot of other science courses. I learned a lot of information I’d never use again (and have since forgotten), particularly in chemistry and physics. I wasn’t eligible to learn the things I wanted to learn until I’d jumped through these hoops.

I hope that these days, with online classes, the tide is starting to turn. I don’t think people should have to take a year of basic biology in order to learn a little about genetics. I don’t think people should have to learn about photosynthesis and the difference between monocots and dicots (those are groups of plants, by the way) in order to learn neurobiology. It is perfectly possible to design science courses for people who are not pre-med or pre-vet undergraduates. But sometimes, when I’m telling people about this great new genetics course I'm teaching and they look slightly alarmed, I'm saddened by the history of how we've traditionally taught science courses.

More than thirty people signed up for the genetics course. I hope I’ve designed something that’s worth their while.

The future of behavior medication?

We don’t actually know how behavior medications work. We know how they change the operations of cells — for example, we know facts like “this medication makes cells slower to recycle this particular chemical.” But we don’t have a good idea of how those cellular-level changes result in behavior-level changes. We don’t know how these medications make individuals feel better.

And that’s a problem, because not every individual responds to a particular behavior med in the same way. A pathologically fearful dog might have nasty side effects on one med, no response to a second, and then respond beautifully to a third. It’s hard on owners to have to try a variety of medications before finding the right one, especially as it takes a month or two to be sure that a particular medication is or isn’t working. (Oh, yeah, and the same is true for humans who use these drugs.)

If we knew how these medications worked, we might be able to figure out who they would work on without so much cumbersome trial-and-error. Imagine taking your shy dog to a veterinary behaviorist, who would do a genetic test and prescribe the right drug based on the results, to go along with behavior modification exercises.

My current work focuses on gene networks that differ in the brain between animals who are shy and aggressive and animals who are confident and friendly. I've always felt that my requests for funding have been a little hand-wavy as I have argued that surely my findings may help us understand behavioral medications better... You know, someday. Someday maybe my findings will help us design better medications, in fact. But that day seemed a really long way off.

Until I read Ed Yong's story “CRISPR’s most exciting uses have nothing to do with gene editing”. CRISPR is a fancy new gene editing technology that has everyone talking about science fiction coming to pass: being able to edit human (and animal) genes to make designer babies (and animals). Edit out the gene variants for genetic diseases before a baby is born! (But hopefully don't slide down the slippery slope to editing height, skin color, eye color, personality...)

But it turns out that CRISPR may have a more subtle use: gene regulation. Soon, scientists may be able use it to tell individual genes to turn on and off (to make more or less of their product). Rather than permanently editing genes in embryos, we could temporarily modify the output of genes in adults. Suddenly my quest to find the sets of genes affecting shyness seems less quixotic. Maybe my discoveries (do you like how I assume I’ll have discoveries? Let’s just pretend it’s a sure thing) won't have to wait for drug discovery work to be useful. Maybe we’ll be able to directly turn the volume up or down on those particular genes, directly affecting pathological shyness.

Scary? Yeah, it's not something I foresee being used therapeutically in the next few years, not until we understand the brain well enough to be able to predict side effects. But it’s really cool to imagine that some day we may have this sort of fine-tuned control over psychological diseases.