Dog star rising: the canine genetic system

Key Points

  • Dogs were domesticated from the grey wolf and domestication occurred just once and in the Old World.

  • Extensive genome resources for dog genetics include meiotic linkage, cytogenetic and radiation hybrid maps, and a 1.5x poodle sequence and 7.8x boxer sequence.

  • Many breeds of dog derive from few founders and/or have gone through population bottlenecks. As a result, many dog breeds have a highly specific set of inherited disease risks.

  • The top ten diseases in purebred dogs include several that are of concern to human health, such as cancer, epilepsy, autoimmune diseases, blindness, cataracts and heart disease.

  • Genetic clustering methods have been used to define relationships among groups of breeds that often correlate with morphological similarity and geographic origins.

  • Linkage disequilibrium extends from 400 kb to 3 Mb in dog breeds, a nearly ten-fold range in just five breeds assayed, which underlines the importance of choosing the right breed for a whole-genome association study.

  • Extensive linkage disequilibrium indicates that up to 100-fold fewer markers will be needed for whole-genome association mapping in dogs compared with humans.

  • Haplotype diversity in dog breeds is low and sharing of haplotypes is extensive, so sets of haplotype tagging SNPs will probably be useful in many dog breeds.

  • Analysis of canid morphology in the Portuguese water dog demonstrates the value of dog breeds for studies in quantitative genetics.

  • In the near future dog populations might be used to map genes important in behaviour.

Abstract

Purebred dogs are providing invaluable information about morphology, behaviour and complex diseases, both of themselves and humans, by supplying tractable populations in which to map genes that control those processes. The diversification of dog breeds has led to the development of breeds enriched for particular genetic disorders, the mapping and cloning of which have been facilitated by the availability of the canine genome map and sequence. These tools have aided our understanding of canine population genetics, linkage disequilibrium and haplotype sharing in the dog, and have informed ongoing efforts of the need to identify quantitative trait loci that are important in complex traits.

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Figure 1: Proportion of purebred dog registrations by the American Kennel Club (AKC).
Figure 2: Grouping of dog breeds by the American Kennel Club (AKC).
Figure 3: Comparative map of dog chromosome 1 and orthologous segments of human chromosomes (Hsa) 18, 6, 9 and 19.
Figure 4: Population structure of 85 domestic dog breeds.
Figure 5: Linkage disequilibrium around a mutation is variable in the population of modern chromosomes that carry the mutation.

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Acknowledgements

N.B.S. is a Waltham Foundation Fellow. E.A.O. gratefully acknowledges support from the NIH and the Burroughs Wellcome Foundation. We thank Ed Giniger, Kerstin Lindblad-Toh, Ewen Kirkness and Francis Galibert for their thoughtful comments and helpful suggestions on this manuscript, and the AKC and Chet Jezierski for use of the copyrighted canine artwork included in figures 2 and 4.

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Correspondence to Elaine A. Ostrander.

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The authors declare no competing financial interests.

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FURTHER INFORMATION

American Kennel Club

Canine Resources at the University of Rennes

Elaine Ostrander's homepage

Genbank

Matthew Breen's homepage

Proposal to sequence the dog genome

The FHCRC Dog Genome Project

The Portuguese Water Dog Georgie Project

UCSC Genome Bioinformatics Site

Glossary

COMPLEX TRAIT

A measured phenotype, such as disease status or a quantitative character, that is influenced by many environmental and genetic factors, and potentially by interactions in and between them.

CANID

A member of the Canidae family of carnivorous mammals that include the wolves, jackals, foxes, coyotes and the domestic dog.

HAPLOTYPE

An experimentally determined profile of genetic markers that is present on a single chromosome of any given individual.

CLADE

A taxon or other grouping of organisms consisting of a single species and its descendents.

RADIATION HYBRID (MAPPING)

A determination of marker order along chromosomes. This is done by assessing the presence or absence of alleles associated with markers in a set of hybrid cell lines, each of which carries a distinct portion of the genome in a rodent background.

ACROCENTRIC

A chromosome in which the centromere lies near to one end, such that one arm of the chromosome is much larger than the other.

FLOW SORTING

The analysis of single cells or subcellular particles by the detection of their light absorption, scattering and/or fluorescence properties as they pass through a laser beam in a directed fluid stream.

DAPI-BANDING

The pattern created from treatment with the sensitive fluorescent probe for DNA, 4′6-diamidino-2-phenylindole-2HCl, used in fluorescence microscopy.

MICROSATELLITE

A class of repetitive DNA that is made up of repeats that are 2–8 nucleotides in length. They can be highly polymorphic and are frequently used as molecular markers in population genetics studies.

SCAFFOLD

A portion of the genome sequence composed of contigs and gaps and reconstructed from end-sequenced whole-genome shotgun clones.

BLASTN

Basic local alignment search tool that compares a nucleotide query sequence against a nucleotide sequence database.

RECIPROCAL ZOO-FISH

Bidirectional heterologous chromosome painting using fluorescence in situ hybrization.

ALU INSERTION

A dispersed, intermediately repetitive 300-bp DNA sequence, found in the human genome in 300,000 copies, that is named after the restriction endonuclease (AluI) that cleaves it.

CONTIG

(and supercontig). A contiguous region of DNA sequence constructed by aligning many sequence reads.

NARCOLEPSY

A sleep disorder characterized by excessive sleepiness, cataplexy, sleep paralysis, hypnologic hallucinations and an abnormal tendency to pass directly from wakefulness into REM sleep.

CYSTINURIA

An inherited abnormality of renal tubular transport of dibasic amino-acids leading to massive urinary excretion of cystine, lysine, arginine and ornithine.

CEROID LIPOFUSCINOSIS

An inherited neurodegenerative disorder associated with the accumulation of an abnormal pigment in the brain called lipofuscin.

LOD SCORE

A method of hypothesis testing that uses the logarithm of the ratio between likelihoods under the null and alternative hypotheses.

FST

A measure of population subdivision that indicates the proportion of genetic diversity found between populations relative to the amount within populations.

LINKAGE DISEQUILIBRIUM

This occurs when the frequency of a particular haplotype for two or more loci deviates significantly from that expected from the product of the observed allelic frequencies at each locus.

ASSOCIATION MAPPING STUDIES

A set of methods used to correlate polymorphisms in genotype to polymorphisms in phenotype in populations.

QUANTITATIVE TRAIT LOCI

Genetic loci or chromosomal regions that contribute to the variability in complex quantitative traits (such as body weight), as identified by statistical analysis. Quantitative traits are typically affected by several genes and can be affected by the environment.

SUBLUXATION

A slight dislocation or disfunction of vertebrae or other joints.

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Sutter, N., Ostrander, E. Dog star rising: the canine genetic system. Nat Rev Genet 5, 900–910 (2004). https://doi.org/10.1038/nrg1492

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