Canine genetics comes of age

doi:10.1016/S0168-9525(99)01958-7

Trends in Genetics

Volume 16, Issue 3, 1 March 2000, Pages 117-124

https://doi.org/10.1016/S0168-9525(99)01958-7 Get rights and content

Abstract

The dog, as human’s favored companion, is unique among animal species in providing new insights into human genetic disease. In this review, we will discuss both the breed and the population structure of dogs and why that makes canines amenable to genetic studies. We will review the current state of the map and discuss the particular disease states in which canines stand to make the greatest contribution to medical genetics.

Section snippets

Studying human genetic disease in dogs

The modern domestic dog has a combination of characteristics that make it truly unique among animal species for the study of human genetic diseases. First, the degree of medical surveillance of the dog is second only to that in humans. As human’s favored companion, the dog’s state of health is observed in intimate detail on a day-to-day basis and its ailments are attended by veterinary specialists using all of the diagnostic approaches of modern medicine. A computerized database of canine

Families, breeds and populations

The second major advantage dogs offer for comparative genetic studies is conferred by the structure of dog populations. The general dog population consists of >300 partially inbred genetic isolates (breeds) and a heterogeneous population of mixed-breed dogs. Gene flow between breeds is restricted by the pedigree barrier (e.g. to be a registered Poodle, the dog’s parents must be registered members of the breed). Of the currently identified genetic disorders in dogs, 46% occur predominantly or

The canine map

The primary tool required for identifying genetic loci of interest is a well-spaced map of highly informative markers. Once a region of linkage has been identified, the route from linked marker to cloning and sequencing the disease gene will be most straightforward if the canine map has been matched to the more well-developed human and mouse maps through the placement of large numbers of conserved genes.

The first sets of anonymous markers that were shown to be linked to one another were

Canine RH map

Whole-genome RH mapping has been shown to constitute a particularly powerful tool for constructing genome maps consisting of both genes and microsatellites. In RH mapping, unlike linkage mapping, non-polymorphic markers (such as gene fragments) can be placed easily on the map, as the technique relies only on detecting the presence or absence of a specific PCR product that has been amplified from the DNA from each hybrid cell line, rather than the separation of different alleles. As a result,

Integrating the linkage and RH maps

Recently, collaborations between our three groups have been established to integrate the existing genetic linkage and RH maps²⁴. The co-ordering of linkage groups and RH groups means that the multitude of RH groups can be quickly condensed to a small number of chromosomes, efficiently increasing the density of markers per chromosome. This approach means that many more markers, as well as genes, are now assigned to each chromosomal group. Because 217 markers typed on the RH panel have also been

Applications of the map to date

The first example of candidate cloning of a canine disease gene was X-linked severe combined immunodeficiency (XSCID) in the Basset Hound. Henthorn et al. mapped the canine XSCID gene to the region of the canine X homologous to that in human XSCID, subsequently showing that, as in humans, the disorder is caused by mutations in the common gamma chain of the interleukin 2 receptor³³. The potential of dog-disease mapping for identifying the genes that underlie human disorders not yet defined at

Conclusions

The manipulation of canine genetics by centuries of human intervention now provides modern biologists with unique opportunities to understand mammalian biology. Because breed structure has created a barrier (albeit an artificial one) to the mixing of genes, the process of trait mapping within single breeds offers the same statistical advantages afforded by the study of human genetic isolates in Finland, Iceland or within the Bedouin tribes of Israel. The number of affected individuals within a

Acknowledgements

We wish to thank C. Mellersh, M. Gibbs, G. Jarvik and E. Giniger for their thoughtful comments, and U. Giger, P. Henthorn and P. Werner for useful comments and assistance in providing illustrative material. We also thank the members of our respective laboratories for their many helpful comments and insights, and for their willingness to share data before publication. The authors acknowledge the support of the American Kennel Club Canine Health Foundation (E.A.O., D.F.P., F.G.), National

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Trends in Genetics

ReviewCanine genetics comes of age

Abstract

Section snippets

Studying human genetic disease in dogs

Families, breeds and populations

The canine map

Canine RH map

Integrating the linkage and RH maps

Applications of the map to date

Conclusions

Acknowledgements

Trends Genet.

Am. J. Hum. Genet.

Genomics

Genomics

Genomics

Genomics

Cell

Genomics

Genomics

History of Dogs in the Early Americas

The Domestic Dog, its Evolution, Behavior and Interactions with People

Origins of the Domestic Dog

Genetics and the Social Behavior of the Dog

Origin, genetic diversity, and genome structure of the domestic dog

BioEssays

Models of human genetic disease in domestic animals

Adv. Hum. Genet.

Research on genetic diseases: reciprocal benefits to animals and man

J. Am. Vet. Med. Assoc.

The importance of the canine model in medical genetics

Bull. Acad. Natl. Med.

Canine Genetic Disease Information System: A Computerized Knowledgebase of Genetic Diseases in Dogs

Congenital Heart Disease

The evolution of specific genetic and environmental counseling in congenital heart diseases

Circulation

Compartment-selective sensitivity of cardiovascular morphogenesis to combinations of retinoic acid receptor gene mutations

Circ. Res.

A single major-gene defect underlying cardiac conotruncal malformations interferes with myocardial growth during embryonic development: studies in the CTD line of keeshond dogs

Am. J. Hum. Genet.

Review
Canine genetics comes of age