Dog Genetics seminars at the University of Iowa, Iowa City, October 2009

Invited speakers

     The University of Iowa recently hosted two of the world leaders in Dog Genetics as back to back speakers: Dr. Elaine Ostrander and Dr. Peter Savolainen (see announcements above).  It is fair to say that such density of genetic information exchange about dogs by the world leading experts in their respective fields is probably a first.  Given the different topics of their respective research, the presentation of data and the discussions after the talks were rather different, Dr. Ostrander’s talk featured the use of Dog Genetics to map complex genetic traits related to leg-length, coat-length and diseases, whereas Dr. Savolainen’s talk focused on the time and place of dog domestication followed by the subsequent dispersal across the world, based on a very large systematic sequencing analysis of hundreds of dog breeds.  Below are the summaries of the two talks.

Dr. E. Ostrander’s presentation:
      The domestic dog offers a remarkable opportunity to disentangle the Genetics of complex phenotypes. To achieve this, over 1000 DNA samples from 147 AKC dog breeds were used to identify candidate genes which are involved in the regulation of dog size and other morphological features such as hip dysplasia, patella luxation, and pancreatitis. Potential genes were also identified for behaviors such as herding and pointing, and for longevity, a breed characteristic inversely correlated with breed size (smaller dogs live longer).  Correlating leg-length with the size of the leg bones revealed a stretch of DNA which contains two collagen genes specifying proteins necessary for bone matrix formation.  In addition, gene mapping data suggest a unique retrogene encoding fibroblast growth factor 4 (fgf4) to be associated with chondrodysplasia, a short-legged phenotype found in Dachshund, Corgi, and Basset Hound.  Another point of interest is the alleged small size of the dog genome with only 19,000 genes. More detailed analysis is now closing the gap with other mammals. Nevertheless, recent analysis characterizes 28 canine-specific gene losses indicating that indeed some genes found in other mammals do not exist in dogs. Comparative genomics can characterize species-specific (and possibly breed-specific) gene gains and losses. As already published recently, coat-growth pattern, length, and curl have been partially characterized in terms of the genes involved. Mutations in only three genes account for most coat phenotypes in purebred dogs in the United States. The seemingly complex phenotypes associated with coat-length and in part used to distinguish between dog breeds can be reduced to the combinatorial effects of only a few genes.

      Dogs, like people, have various cancers.  Histiocytic sarcoma (HS; previously called malignant histiocytosis) is breed specific, with Bernese Mountain Dogs, Rottweilers, and Retrievers having a high prevalence with a frequency of approximately 25% in the Bernese Mountain Dog breed. Using genetic information on Bernese Mountain Dogs, Dr. Ostrander and colleagues propose an oligogenic transmission mode for this disease and another cancer found with high incidence in Shelties and Scotties. A paper on the complex inheritance of the cancer in these later breeds is now in preparation.  Further analysis is needed to localize the genes for HS in the Bernese Mountain Dog, leading to advances in our knowledge of histiocyte diseases and other cancers in dogs and humans and, ultimately, to help in early diagnosis and perhaps even treatment.  A simple fact that enhances the ability of this group for these studies is that the mapping density to figure out where mutated genes are located is easier to achieve in dogs compared to humans.

      Interesting discussions on dog genome related problems abounded during the dinner and ideas concerning dog genome analysis with respect to bone density related to the human mutation affecting bone density were discussed.  It was also agreed that future work is needed to expand the suggestions based on gene mapping by analyzing the functional interactions of those genes in mutant mice and a project is currently discussed to generate mice with short and long legs, assuming that the genes identified in dogs have similar effects in mice.  At least the genes related to coat-length, texture and curls are already identified in mice as being related to a similar phenotype.

Dr. P. Savolainen’s presentation
      Dr. Savolainen reported on the findings based on a partial analysis of the mitochondrial DNA (mtDA) of  1,543 dogs for a comprehensive picture of geographical diversity, and on an indepth study of the mtDNA of 169 dogs selected for being representative of mtDNA diversity.  Based on this large scale analysis his group can for the first time provide a detailed picture of the place and time of domestication of the dog. According to this team’s data, the dog has a single origin in southern China less than 16,300 years ago.  This conclusion is based on the fact that most dogs share the clades A,B and C in the same proportions across Eurasia. The complete mtDNA genome analysis shows that clades A, B and C consist of several subgroups. (Clade A has 6 major subclades, Clade B and C have 2 subclades each) with a total of  10 subclades (haplogroups). The genetic diversity follows a gradient, from maximum levels at one end of the continent South of the Yangtze River, decreasing through East Asia and Eurasia to reach the lowest levels in Europe at the other end of the continent. The full range of all 10 haplogroups was only found south of the Yangtze River.  Fewer haplotypes were found in Central China, and even fewer in North China and only 4 haplogroups were found in Europe. The results indicate that the domestic dog may have originated from several hundred wolves. The place and time coincide approximately with the origin of rice agriculture, suggesting that the dogs could have originated among sedentary hunter-gatherers or early farmers, and the numerous founders indicate that wolf taming was an important culture trait at the time.

      The subsequent discussion was centered around the problems of how to distinguish spread from southern China from dilution of the southern Chinese dog genes by repeated  breeding with wolves (a distinction that can not be made at the moment) and how reverse mutations in the genes should be identified (they can not be, thus generating some noise in the data).  During the discussion, data of Dingoes were presented which showed that all Dingoes are derived from a very small and genetically homogeneous pool.   The discussion also revolved around the suggested use of early domesticated wolves as food and it was noted that this tradition is not only part of the Chinese culture but is found in various tribes of Africa as well.  Fossil evidence showing cooked dog bones is now needed to support this hypothesis. Another point brought up was the claim that African dogs have a somewhat similar haplotype diversity as Chinese dogs.  However, this study was only comparing the Dr. Savolainen's et al. previous publication (2002) and does not refute the more extensive recent data just published.

 © Dr. Bernd Fritzsch 2009 
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