Dog Genetics

Dr. Philip Grossi
Wednesday, 16 February 2011

I enjoyed watching the variety of dogs from Pekingese and Pomeranians to Great Dames and Mastiffs at the Westminster Dog Show the last few nights. I began to think of the important contribution that dog genetics is making and will make to understanding  the genetic underpinning of human illnesses. The dozen most common illnesses in dogs are also commonly found in humans. Some examples are cancer, allergy, heart disease, and epilepsy. Furthermore, dogs are highly inbred for specific traits  such as size, coat pattern, color, and behavior such as pointing, retrieving, herding and swimming. In addition, dogs have large families with clearly documented genealogies. The inbreeding is especially important because each dog breed in an isolated population that typically goes back only a few hundred years, which limits the chance of spontaneous mutations as well as mutations from outbreeding. Also, dogs live in the same environment as humans do and are thus exposed to the same risk factors. All of these features make dog genetics extremely valuable and powerful in illuminating human illnesses.

There was a lot of skepticism about this conclusion until 1998 when Emmanuel Mignot at Stanford found the gene that causes narcolepsy in dogs.  His group found causative mutations in the Hcrtr 2  gene of Doberman pinschers, Labrador retrievers, and dachshunds. This opened up a whole new molecular pathway involving sleep and researchers minds were also opened to the importance of dog genetics. Indeed, this discovery was important in convincing the National Human Genome Research Institute to support the sequencing of the canine genome, which was published in December 2005.

illustration to dog genetics blogThe power of dog genetics comes largely from the inbreeding and this is especially evident in complex disorders.  In a given human illness there may be many responsible genes, but in dogs of a particular breed you will find exactly the same mutation as the cause in a small animal sample size because they have descended from an isolated inbred population. This characteristic of dog genetics is very powerful. If you find the same illness in two different breeds, you can find another causative mutation which leads to additional insights into the molecular pathways involved in the causation of the illness in question. These techniques can also be used to sort out how different breeds are related.  The more variants that are shared, the closer are the breeds.  This has led to a project called PhyDo which has revealed that 150 or so breeds recognized by the American Kennel Club recognizes break down into five genetically defined groups that can be further subdivided.

Some non-psychiatric illnesses that are currently under investigation in dogs include bladder cancer, squamous cell carcinoma, skin or coat color, atopic dermatitis, and neural tube defects. Some efforts are now being made to track down genes related to behavioral characteristics such as pointing (lifting a paw and holding it in the direction of a quarry) or "cocker rage" which is sudden unprovoked episodes of rage and aggressive behavior in generally friendly docile animals.  This occurs in English cocker spaniels and  English springer spaniels, as well as some other breeds.  The hope is that this will get the researchers close to the gene or genes involved and can shine a light on rages in those who have schizophrenia, bipolar disorder, anxiety disorders, or depressions. 

Going to the dogs is acquiring a whole new meaning.

Collective Intelligence

Dr. Philip Grossi
Monday, 14 February 2011

In 1904 Charles Spearman published his findings on intelligence which showed that cognitive performance on one test  tended to predict performance on other tests in spite of huge differences in content, methods of administration, and skill tested. He concluded that there was a single general intelligence factor for which he coined the term g  factor.  Tests of intelligence are valuable because they can be administered in an hour or two and have wide utility in predicting school performance, success in occupations, etc.

illustration to collective intelligence blogThe complexity of cross-domain problems we face today require specialized knowledge and expertise in disparate areas and thus their solution requires more team effort than in the past. Therefore, elucidation of the factors influencing group performance is quite important if we want to make predictions similar to those for general intelligence. Now comes Anita Woolley and colleagues who published last year in Science the results of a study of "collective intelligence" which is called the c factor. They found evidence of a collective intelligence factor that explains a group's superior performance on a variety of tasks.  The c factor is correlated with social sensitivity of the group members, the equality of turn-taking in conversations, and the proportion of females in the group. Contrary to expectations, neither the average intelligence of the group nor the smartest individual in the group were the best predictor of the group's performance.  They also found that group cohesion, motivation, and satisfaction did not predict group performance.

These conclusions were drawn from two parts of a study with a sample size of 120 individuals drawn from the Boston area and 579 from the Boston and Pittsburgh areas.  In the first part of the study the 120 people were randomly assigned to teams of three who then worked on a variety of tasks. They found that performance on one task predicted performance on another task.  This was directly analogous to the approach that Spearman took regarding general intelligence over one hundred years ago.  The researchers then enrolled 579 people from Boston and Pittsburgh and assigned them to groups of two to five individuals and found that "social sensitivity", the degree of turn-taking in conversation, and the proportion of women in the group correlated most positively with collective intelligence. (Social sensitivity was measured by showing a photograph of a face cropped to show the two eyes and asking the participant to infer what the individual was feeling).

I think this research is significant and provides a guide to the formation of groups tasked to solve particular problems.

Bipolarity:The Positive

Dr. Philip Grossi
Monday, 14 February 2011

When I make the diagnosis of bipolar disorder and discuss it with a patient, I am often confronted with a negative reaction. Worries of the associated stigma are expressed and stereotypes derived from the lay press are expressed freely as are insurance and employment worries.  This is particularly unfortunate since bipolar spectrum disorder is present in 4 to 6 % of the population and has a lifetime suicide rate of between 10 to 15%. It is also associated with a higher rate of medical comorbidities. 

The fact that this mental illness is very treatable and can have positive features is often overlooked by patient and treating professional alike.  In the previous blog the association of bipolarity and creativity was exemplified in the life of Goethe.  Another characteristic that is shown in depressed people more than non-depressed people is realism.  Depressed people assign errors to themselves more often that control subjects. This realism may be an insight in depression. The reverse is true in mania.

The positive aspects of bipolar spectrum disorder should be stressed because social stigma influences quality of life in psychiatric patients with this disorder.  They have to cope with their illness as well as the negative attitudes in the community. Often these patients are seen as somewhat responsible for their illness and are not accepted as a patient with a physical illness would be.  They are often met with anger, seen as dangerous, and infrequently offered empathy.  A more balanced and nuanced view of bipolar spectrum disorders will help in the treatment of these individuals..