Dogs

Generalities

The dog is the result of the domestication of the wolf. All the current breeds, although resulting from different crossbreeds, share common and recent ancestors. The dog is the mammal species with the greatest morphological and behavioural diversity, with more than 350 breeds listed. This diversity results from the genomic dynamics of the dog maintained by the selective action initiated by man over the last century. The objective has been to favour the setting of very different anatomical, aesthetic or functional criteria in order to meet the varied expectations of owners. Thus, some breeds are specialized for hunting, guarding and transport, while others are maintained for their aptitude for herding. Recent breeding practices have mainly emphasized the almost systematic use of a few champion stallions (founding effect), the strict selection of their descendants and the repeated use of inbreeding (racial barrier) to quickly establish the desired characteristics.

This resulted in increasing the genetic homogeneity of individuals within the same race while maintaining inter-racial diversity. As a result, today’s dog population is made up of many breeds with common roots, each of which can be considered, at the genetic level, as an isolate suitable for genetic analysis. These analyses are made possible by the existence of an intra- and inter-racial polymorphism resulting from the genetic drift mechanism. In parallel with the selection of these desired traits, traits invisible at birth and detrimental to the health of the animals have been unintentionally established. These alleles were unintentionally co-selected because they were spatially close to the alleles governing the desired traits. The current gene pool of each dog breed therefore contains a panel of deleterious alleles, or inappropriate combinations of alleles, responsible for organic dysfunctions. Thus, hundreds of monogenic or complex hereditary diseases are recorded in dogs. Most of them are identical to those described in humans and are therefore excellent physiopathological models.

Since the end of the 1990s, the dog has thus emerged as the model of choice for the identification of the alleles responsible for the extreme phenotypic variability observed in this species, whether physiological or pathological in nature. Since 2005, this identification has been greatly enhanced by the availability to the scientific community of the complete sequence of the canine genome, and by the organization of the fields and laboratories concerned into study groups and international consortiums.

Name : Canis (lupus) familiaris (Pang et al., 2009, regarding its lupine origin)
Phylogenetic classification : mammal of the order Carnivore, family Canidae, species Canis lupus and subspecies Canis lupus familiaris
Genome sequencing complete since 2005 (Lindblad-Toh et al., 2005)
Size of the genome : 2,4 billion pb on 78 chromosomes (38 pairs of acrocentric autosomes + X, Y).
Number of genes : about 20.000

Reproduction

The female’s cycle is mono-estrian, seasonal and lasts about 6 months. The dog’s heat therefore occurs once or twice a year. There are 4 periods in the dog’s cycle.

Proestrus : period when the female attracts males but does not accept mating. On average, it lasts 9 days but can go from 2 to 17 days. The most frequent signs of proestrus are an edema of the vulva and a sero-blood flow.

Estrus : the female accepts the male during this period. It normally lasts 9 days but can range from 3 to 21 days.

Diestrus : the female is no longer receptive to the male and rejects coitus. Physiologically, it corresponds to the establishment of the corpus luteum (metestrus) and then to its full functioning (di-estrus, production of progesterone). During this long phase of about 2 months, the female undergoes progesterone peaks. This can lead, even in the absence of fertilization, to the expression during this period of hormone-dependent signs normally associated with gestation (maternal behavior, lactation).

Anestrus : phase of sexual inactivity and ovarian rest (absence of folliculogenesis and corpus luteum). It lasts between 30 and 230 days depending on the breed. Puberty is reached when the puppy reaches about 2/3 of its adult weight. It therefore occurs at the age of 6 to 20 months depending on the size of the animal as defined by breed criteria.

Gestation lasts an average of 62 days and parturition is generally unassisted except for brachycephalic dogs (short, broad head). The size of the litters is very variable: from 1 to sometimes more than 12 puppies.

To date, no hormonal treatment allows reliable control of the female sexual cycle, prohibiting any experimental programming of births.

Tools

Collection of irradiation hybrids used as a reference for the international community for the location and identification of genes, especially those involved in diseases with genetic components. The map of irradiation hybrids contains 3270 markers with a resolution of 1 marker per megabase (Guyon et al., 2003). This map also allowed the identification of regions of conservation or breakage of synteny between the human and canine genomes.
High-resolution map with more than 10,000 markers corresponding to canine genes for which all human orthologs genes are identified (Breen et al., 2004; Hitte et al., 2005)
The 7.6 X sequence of the canine genome is available since 2005 (Lindblad-Toh et al., 2005).
Various microsatellite markers are available for linkage or association studies (Sargan et al., 2007).
An analysis of genetic diversity in different breeds of dog, as well as breeds of wolf and coyote, identified more than 2.5 million SNP (Lindblad-Toh et al., 2005).
Studies conducted on monogenic diseases for which the dog is a model organism have shown great promise for initiating gene therapy trials in humans (Leber's amaurosis, Duchenne muscular dystrophy: for a review see Vanbelle 2008).

Databases

Genomic databases :

http://www.ensembl.org/Canis_familiaris/Info/Index

http://www.genome.ucsc.edu/

http://www.ncbi.nlm.nih.gov/genome/guide/dog/

http://autograph.genouest.org/

http://dogs.genouest.org/rh-server.html

SNPs library:

https://www.broadinstitute.org/disease-research/dog-snps-canfam-10

Phenotypic database :

http://www.vet.cam.ac.uk/idid/

Infrastructures

Experts

Bibliography

Guyon R. et al. (2003). “A 1-Mb Resolution RH map of the canine genome”
Proc Natl Acad Sci. 100, 5296-5301

Breen M. et al. (2004). “An Integrated 4249 marker FISH/RH Map of the canine genome.”
BMC Genomics, 5, 65

[FR] Galibert F. et al., (2004). “Le chien, un modèle pour la génétique des mammifères.”
Médecine Sciences 20, 761-766

Hitte C. et al. (2005). “Facilitating genome navigation: survey sequencing and dense radiation-hybrid gene mapping.”
Nat Rev Genet. 8, 643-8

Lindblad-Toh K. et al. (2005). “Genome sequence, comparative analysis and haplotype structure of the domestic dog.”
Nature 438, 803-819

Sargan D. (2007). “An Extended Microsatellite Set for Linkage Mapping in the Domestic Dog.”
J of Heredity. 98, 221-231

[FR] Vanbelle P. (2008). “Intérêt du modèle canin en thérapie génique.”
Thèse de doctorat vétérinaire. Ecole Nationale Vétérinaire d’Alfort. p 194

Pang J.F. et al. (2009). “mtDNA Data Indicates a Single Origin for Dogs South of Yangtze River, less than 16,300 Years Ago, from Numerous Wolves.”
Mol Biol Evol epub

http://dogs.genouest.org

http://www.broad.mit.edu/mammals/dog

Public information base of the LUPA European consortium: http://www.eurolupa.org