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By Mark W. Neff, Ph.D.
Canine Genetics Unit
Veterinary Genetics Laboratory
University of California, Davis.

Biology of the Tibetan Terrier: As with all breeds, the Tibetan Terrier is defined by a set of inherited attributes that have been selectively bred for over many generations. In addition to these attributes, which include a long, soft coat and a robust temperament, other characteristics, sometimes undesirable, have also become part of the breed’s genetic legacy. These secondary characteristics apparently include a predilection for missing teeth, a predisposition to separation anxiety, an overly sensitive immune system, and an incidence of several single-gene diseases. The perceived biological strengths and weaknesses of a breed collectively comprise the breed’s ‘phenome’ – this is the sum total of traits that distinguish a breed from all others, and make the breed of particular interest to biologists. Remarkably, this phenotypic breed profile will one day be understood at the level of the DNA sequence through genetics.

The Geneticist’s Perspective: The study of genetics is about understanding inherited differences, about viewing the biological world in terms of contrasts. Geneticists are limited to studying differences within a species where patterns of inheritance can be observed in families and populations. A geneticist aims to tie a difference in phenotype (i.e., an observable trait like coat color) to a difference in genotype (i.e., a readable change in DNA sequence). Understanding the pattern of inheritance can lead to identifying a causative gene, which in turn can be translated into a DNA test for breeders. The causative gene can also provide access to additional genes through various laboratory methods. This broadening of genetic knowledge is important because a gene impacts just a single step in an otherwise complex biochemical pathway (e.g., producing and distributing the pigments of coat color). Elucidating the full series of gene-defined steps in a given biochemical pathway is really the ultimate aim of genetics.

Current Events in Canine Genetics: Today is an extraordinary time in canine genetics research. The National Institutes of Health (N.I.H.), the U.S.’s premiere funding agency for basic research, has committed $46 Million to the sequencing of the dog genome. This effort is currently ongoing at the Whitehead Institute (M.I.T.), one of the top genome centers in the world. Researchers are already taking advantage of the sequence that is being deposited nightly into public databases. By the summer of 2004, canine researchers will have access to the same technology platform that is currently available for human genetics. This new sequence-based platform will revolutionize dog genetics and accelerate the pace of discovery. It will make possible entirely new experimental approaches in the dog, allowing geneticists to move from traditional family-based studies to more powerful population-based approaches. It will have the added effect of attracting scientists from other fields and disciplines, which will invigorate canine genetics and stimulate new ideas and new collaborations.

Implications of a Dog Genome DNA Sequence: Perhaps the most noticeable effect that a complete genome sequence will have on laboratory practices is that scientists will spend more time at the computer and less time at the laboratory bench. The implications for breeders will be more striking. The rate of gene discovery will be greatly accelerated, and hence new DNA tests will become available at a greater pace. Breeding strategies based upon tests are not straightforward, and the currently unmet need for genetic counseling will become an even greater demand. Now is the time for breeders and breed clubs to begin preparing for these advances.

The Domestic Dog – A New Model Organism: Although the NIH will be delighted to see canine health improved by genetic discoveries, the millions of dollars put forth by the NIH to sequence the dog genome represents an enormous investment in the dog as a new model organism, one that is widely recognized for unparalleled biological opportunities. Breeds of dog show profound differences in size, shape and behavior, and understanding the nature of these differences will shed light on some of biology’s most fundamental mysteries. Understanding phenotypic diversity in the dog will provide novel insights into development, evolution, and behavior.

The Primary Importance of Breeders & Owners: Canine geneticists study phenotypes in dogs in the same manner that human geneticists study phenotypes in man – by tapping variation that already segregates in families and populations. Fully exploiting this phenotypic diversity requires the full participation of breeders and owners. Breeders and owners control that which is necessary for genetic research. Breeders and owners can provide the genealogical records that describe the relatedness of animals in a study. Breeders and owners, who know their animals better than anyone else, can provide information describing the differences found within litters, and the characteristics of individual dogs. Finally, breeders and owners can contribute the DNA samples that form the basis of a genetic project.

Toward these ends, the Tibetan Terrier community has excelled, both in terms of generating discussion of traits and collecting DNA samples. Owing largely to a well-informed, well-organized leadership as well as an unsurpassed level of international cooperation, the Tibetan Terrier community has already laid a groundwork that will drive future genetic studies. The large-scale collection of blood samples and their deposition into a central DNA repository at the University of Missouri is a key achievement, one that will certainly attract the interest of academic researchers. These efforts will hopefully continue, and perhaps even gain in momentum.