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Let sleeping dogs lie?

Nature Genetics volume 23, pages 3–4 (1999)Cite this article

The narrow range of phenotypic variation observed in dogs of any single breed results from the deliberate crossing of closely related individuals. This often leads to the association of specific recessive, inherited diseases with specific breeds. Mignot and colleagues have exploited this aspect of canine population biology by establishing a colony of Doberman Pinschers which segregates the canine narcolepsy locus, designated canarc-1, as an autosomal recessive, fully penetrant trait3,4. Physiological and pharmacological studies of these dogs suggest a close similarity between the canarc-1 phenotype and human narcolepsy5,6.

Lin et al. cloned canarc-1 by exploiting both the population structure of the domestic dog and orthologous synteny between the canine and human genomes. A combination of limited founder pool, genetic drift in a small population and breeding of closely-related individuals means that dog breeds are akin to geographically isolated human populations, such as those in remote portions of Iceland or Finland. As predicted then, all affected Dobermans carried the same underlying mutation, and fine-mapping with recombinants was easily accomplished with a number of seemingly unrelated Doberman families. Next, the region of canine chromosome 12 to which the canarc-1 locus mapped was found to bear orthologous synteny with a well-mapped region of human 6p21 (Refs 1,9). This greatly facilitated the development of a BAC contig across the region and the identification of the gene encoding the hypocretin type 2 receptor (Hcrtr2) as a plausible candidate.

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Figure 1: A Doberman Pinscher affected with inherited narcolepsy.
Figure 2: Partial pedigree of Doberman Pinscher family segregating canarc-1 .

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Authors and Affiliations

  1. Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D4-100, Seattle, 98109-1024, Washington, USA

    Elaine A Ostrander

  2. Basic Science Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D4-100, Seattle, 98109-1024, Washington, USA

    Edward Giniger

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  1. Elaine A Ostrander
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  2. Edward Giniger
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Ostrander, E., Giniger, E. Let sleeping dogs lie?. Nat Genet 23, 3–4 (1999). https://doi.org/10.1038/12591

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