MOTIVATION:Understanding kinship relationships is fundamental to genetic research, particularly in the context of genetic linkage studies and population genetics. Pedigree design and analysis are a prerequisite for these investigations. The legacy kinship2 CRAN package has been a cornerstone in this area; however, the need for handling larger and more complex datasets necessitates an updated, flexible, and user-friendly toolset. To address this issue, we present Pedixplorer, a novel Bioconductor package designed to enhance kinship analyses with modern functionality and usability, especially in large multigeneration complex pedigrees with inbreeding loops, which are frequently seen in domestic animal breeding. RESULTS:Pedixplorer builds upon the robust foundation of kinship2, integrating Bioconductor standards and most recent programming practices. Its core component is the S4 Pedigree object, facilitating efficient representation of complex pedigrees. The new functions enable automatic querying, filtering, and trimming of large pedigrees, while the graphical functions have been rewritten for better customization in pedigree visualizations. Additionally, Pedixplorer offers a comprehensive Shiny application, accessible both locally and via a dedicated website, allowing non-R users to easily create, filter, and customize pedigrees. AVAILABILITY AND IMPLEMENTATION:The Pedixplorer package is freely available at: https://www.bioconductor.org/packages/release/bioc/html/Pedixplorer.html with additional documentation at https://louislenezet.github.io/Pedixplorer. A user-friendly web application is available at: https://pedixplorer.univ-rennes.fr.

Hereditary sensory and autonomic neuropathies (HSAN) represent a group of genetic diseases affecting the peripheral nervous system. In humans, at least 16 loci have been associated with the disorder but do not explain the disease origin of all patients. In dogs, similar conditions have been documented for decades in various breeds with a severe impact on life quality and are often referred to as acral mutilation syndrome (AMS). Causal variants in three genes have been identified to date, suggesting larger genetic heterogeneity in the dog population. Our aim was to explain the genetic etiology of an early-onset HSAN/AMS in a purebred German Spitz. The affected dog showed progressive loss of pain sensation in the distal extremities, which led to intense licking, biting, and self-mutilation of digits and paw pads. Whole-genome sequencing identified a single candidate causal variant on chromosome 4 in the RETREG1 gene (c.656C>T, p.Pro219Leu). This missense variant was previously recognized as deleterious in a mixed breed dog family with similar clinical signs. Haplotype analyses and targeted genotyping revealed a likely German Spitz ancestry of these mixed breed dogs. Further screening of an extensive cohort of ~900 000 dogs of various breeds hinted at the variant allele origin in the German Spitz breed. Disruption of RETREG1 inhibits endoplasmic reticulum turnover and leads to neuron degeneration. Our findings provide evidence that this variant underlies the recessive form of HSAN/AMS in the German Spitz and support the use of whole-genome sequencing-based veterinary precision medicine for early diagnosis and prevention via a genetic test.

Bernese mountain dogs are a large dog breed formed in the early 1900s in Switzerland. While originally farm dogs that were used for pulling carts, guarding, and driving cattle, today they are considered multi-purpose companion and family dogs. The breed is predisposed to several complex diseases, such as histiocytic sarcoma, degenerative myelopathy, or hip dysplasia. Using whole-genome sequencing (WGS) data, we assessed the genomic architecture of 33 unrelated dogs from four countries: France, Sweden, Switzerland, and the United States. Analysis of runs of homozygosity (ROH) identified 12,643 ROH with an average length of 2.29 Mb and an average inbreeding coefficient of 0.395. Multidimensional scaling analysis of the genetic relatedness revealed limited clustering of European versus USA dogs, suggesting exchanges of breeding stock between continents. Furthermore, only two mtDNA haplotypes were detected in the 33 studied dogs, both of which are widespread throughout multiple dog breeds. WGS-based ROH analyses revealed several fixed or nearly fixed regions harboring discreet morphological trait-associated as well as disease-associated genetic variants. Several genes involved in the regulation of immune cells were found in the ROH shared by all dogs, which is notable in the context of the breed's strong predisposition to hematopoietic cancers. High levels of inbreeding and relatedness, strongly exaggerated in the last 30 years, have likely led to the high prevalence of specific genetic disorders in this breed.

Some Border Collies, essentially males on average 4-year-old, exhibit focal or generalized retinal atrophic lesions. A following survey revealed progressive lesions and histopathology examination confirmed retinal degeneration. The hypothesis of a X-linked inheritance is supported by a genetic linkage study highlighting the X chromosome. Whole genome sequencing («short read » ) of several dogs identifies variants segregating as expected. The «long read » would allow the identification of structural variants. Variability in the phenotype might induce difficulties to point out common variants in affected dogs. Thus, a strict selection of the cases has been performed. In addition, the selection of breeding dogs on the basis of the X-linked inheritance by the French Border Collie Kennel Club enabled to decrease the frequency of the affected dogs from 20% (2001) to 7,4% (2019).

Les atrophies progressives de la rétine chez le chien sont initialement explorées par un examen clinique approfondi et des examens complémentaires selon nécessité. La description d’un phénotype typique est une condition nécessaire pour exploiter les données fournies par l’étude des généalogies de sujets d’intérêt. Malgré des signes physiques comparables, des évolutions différentes doivent interroger le clinicien, car homogénéité ophtalmoscopique ne signifie pas homogénéité génétique. Jointe à une description fiable, interprétable des signes cliniques, c’est la connaissance aussi détaillée que possible de la physiopathologie de l’affection qui permet d’entreprendre son étude génétique moléculaire dans de bonnes conditions, afin de choisir les meilleures stratégies d’étude (gènes candidats, analyses de liaison, séquençage du génome entier) pour identifier les mutations impliquées. Ces différentes étapes ont pour but de valider et proposer des tests génétiques diagnostiques, dont les résultats doivent toujours être confrontés à ceux de la clinique. Les modalités de ces stratégies sont illustrées à l’aide d’exemples de dégénérescences rétiniennes dans différentes races.

Histiocytic sarcoma (HS) is a rare but aggressive cancer in both humans and dogs. The spontaneous canine model, which has clinical, epidemiological, and histological similarities with human HS and specific breed predispositions, provides a unique opportunity to unravel the genetic basis of this cancer. In this study, we aimed to identify germline risk factors associated with the development of HS in canine-predisposed breeds. We used a methodology that combined several genome-wide association studies in a multi-breed and multi-cancer approach as well as targeted next-generation sequencing, and imputation We combined several dog breeds (Bernese mountain dogs, Rottweilers, flat-coated retrievers, and golden retrievers), and three hematopoietic cancers (HS, lymphoma, and mast cell tumor). Results showed that we not only refined the previously identified HS risk CDKN2A locus, but also identified new loci on canine chromosomes 2, 5, 14, and 20. Capture and targeted sequencing of specific loci suggested the existence of regulatory variants in non-coding regions and methylation mechanisms linked to risk haplotypes, which lead to strong cancer predisposition in specific dog breeds. We also showed that these canine cancer predisposing loci appeared to be due to the additive effect of several risk haplotypes involved in other hematopoietic cancers such as lymphoma or mast cell tumors as well. This illustrates the pleiotropic nature of these canine cancer loci as observed in human oncology, thereby reinforcing the interest of predisposed dog breeds to study cancer initiation and progression.

Histiocytic sarcoma (HS) is a rare but aggressive cancer in humans and dogs. The spontaneous canine model, with the clinical, epidemiological and histological similarities with human HS and specific breed predispositions, is a unique model/opportunity to unravel the genetic bases of this cancer. In this study, we aimed to identify germline risk factors associated with the development of HS in canine predisposed breeds. We used a methodology that combined several genome-wide association studies in a multi-breed and multi-cancer approach, as well as targeted next generation sequencing, and imputation combining several breeds (Bernese mountain dog, Rottweiler, flat coated retriever and golden retriever) and three haematopoietic cancers (HS, lymphoma and mast cell tumor). Results showed that we not only refined the previously identified HS risk CDKN2A locus but we identified new loci on canine chromosomes 2, 5, 12, 14, 20, 26 and X. Capture and targeted sequencing of specific loci pointed towards the existence of regulatory variants in non coding regions and/or methylation mechanisms linked to risk haplotypes, leading to strong cancer predispositions in specific dog breeds. Our results showed that these canine cancer predisposing loci appear to be due to the additive effect of several risk haplotype involved also in other haematopoietic cancers such lymphoma or mast cell tumor, illustrating the pleiotropic nature of these canine cancer loci as observed in human oncology, thus reinforcing the interest of predisposed dog breeds to study cancer initiation and progression.

Soixante-dix-huit (78) examens oculaires ont été réalisés chez soixante-dix (70) chiens de berger de Picardie, dont 43 femelles et 27 mâles âgés de 6 semaines à 12 ans. L’examen clinique effectué par ophtalmoscopie indirecte a permis d’identifier plusieurs types de lésions du fond d’œil : 28 observations de rétinopathie focale (dont 22 bilatérales), 8 de dégénérescence rétinienne généralisée, 3 de dysplasie rétinienne multifocale ; des plis rétiniens du jeune âge ont été relevés chez 6 chiots. Parmi ces chiens, 14 ont subi un examen électrorétinographique (ERG), 2 une angiographie fluorescéinique (AF), 2 une tomographie en cohérence optique (OCT) ; un examen histopathologique a pu être effectué chez un chien aveugle âgé de 9 ans atteint de rétinopathie, ainsi que chez un chiot amblyope âgé de 7 semaines, chez qui l’examen en microscopie électronique à transmission (MET) a aussi été réalisé. Par ailleurs, un pedigree de 154 chiens incluant 63 sujets atteints ou suspects de rétinopathie, dont certains font partie de la présente étude, a été constitué. Les résultats attestent d’animaux jeunes ou jeunes adultes préférentiellement atteints de rétinopathie focale, d’une évolution lésionnelle avec possible participation choroïdienne (AF) ; ils ne montrent en revanche ni prédisposition de sexe, ni correspondance constante entre la gravité des lésions, celle du déficit visuel et les modifications de l’ERG. L’examen en OCT confirme le caractère bulleux, évolutif des lésions focales de décollement rétinien séreux, et met en évidence à ce niveau des modifications des zones ellipsoïdes (ZE) et d’interdigitation (ZI) des photorécepteurs (gonflement précoce), ainsi qu’un amincissement de la couche nucléaire externe (CNE) ; la segmentation de la neurorétine non décollée est normale et on observe des lacunes dans la couche des cellules ganglionnaires. L’examen histologique chez le chiot amblyope âgé de 7 semaines, dont le père était atteint de rétinopathie focale, met en évidence des modifications précoces de la couche des articles externes et un amincissement de la CNE. La MET confirme une atteinte dégénérative précoce des cellules ganglionnaires avec vacuolisation. Celui des globes oculaires du chien aveugle âgé de 9 ans révèle une atrophie rétinienne évoluée généralisée. Le pedigree de 154 sujets apparentés permet de formuler l’hypothèse d’une transmission autosomique récessive.

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal disorders eventually leading to blindness with different ages of onset, progression and severity. Human RP, first characterized by the progressive degeneration of rod photoreceptor cells, shows high genetic heterogeneity with more than 90 genes identified. However, about one-third of patients have no known genetic causes. Interestingly, dogs are also severely affected by similar diseases, called progressive retinal atrophy (PRA). Indeed, RP and PRA have comparable clinical signs, physiopathology and outcomes, similar diagnosis methods and most often, orthologous genes are involved. The many different dog PRAs often segregate in specific breeds. Indeed, undesired alleles have been selected and amplified through drastic selection and excessive use of inbreeding. Out of the 400 breeds, nearly 100 have an inherited form of PRA, which are natural animal models that can be used to investigate the genetics, disease progression and therapies in dogs for the benefit of both dogs and humans. Recent knowledge on the canine genome and access to new genotyping and sequencing technologies now efficiently allows the identification of mutations involved in canine genetic diseases. To date, PRA genes identified in dog breeds correspond to the same genes in humans and represent relevant RP models, and new genes found in dogs represent good candidate for still unknown human RP. We present here a review of the main advantages of the dog models for human RP with the genes already identified and an X-linked PRA in the Border collie as a model for orphan X-linked RPs in human.

In humans, hereditary sensory neuropathies (HSN), also known as hereditary sensory and autonomic neuropathies (HSAN), constitute a clinically and genetically heterogeneous group of disorders characterized by progressive sensory loss, often accompanied by chronic skin ulcerations and nail dystrophic changes. To date, although around 20 genes have already been discovered, they do not explain the genetic causes of all patients. In dogs, similar neuropathies are also diagnosed, several breeds being predisposed to specific forms of the disease. Indeed, the breed specificity of most canine genetic diseases is due to the small numbers of founders and high levels of inbreeding. Recent knowledge and tools developed to study the canine genome efficiently allows deciphering the genetic bases of such diseases. To date, a dozen breeds are recognized to develop specific HSN. For the Border collie and hunting dog breeds, the genes involved have recently been discovered. Other affected breeds thus constitute potential genetic models, with new genes to be found in dogs that can be considered as candidate genes for human HSAN/HSN. Here, we review the different forms of human and canine HSAN/HSN and we present a novel form in Fox terrier cases, highlighting the advantages of the dog model for such rare human diseases.

In humans, hereditary sensory neuropathies (HSN), also known as hereditary sensory and autonomic neuropathies (HSAN), constitute a clinically and genetically heterogeneous group of disorders characterized by progressive sensory loss, often accompanied by chronic skin ulcerations and nail dystrophic changes. To date, although around 20 genes have already been discovered, they do not explain the genetic causes of all patients. In dogs, similar neuropathies are also diagnosed, several breeds being predisposed to specific forms of the disease. Indeed, the breed specificity of most canine genetic diseases is due to the small numbers of founders and high levels of inbreeding. Recent knowledge and tools developed to study the canine genome efficiently allows deciphering the genetic bases of such diseases. To date, a dozen breeds are recognized to develop specific HSN. For the Border collie and hunting dog breeds, the genes involved have recently been discovered. Other affected breeds thus constitute potential genetic models, with new genes to be found in dogs that can be considered as candidate genes for human HSAN/HSN. Here, we review the different forms of human and canine HSAN/HSN and we present a novel form in Fox terrier cases, highlighting the advantages of the dog model for such rare human diseases.

About this supplement These abstracts have been published as Canine Genetics and Epidemiology Volume 5 Supplement 2, 2018: Selected canine abstracts from the Companion Animal Genetic Health conference 2018 (CAGH 2018): Canine Genetics and Epidemiology. A meeting report from the conference has been published as Canine Genetics and Epidemiology Volume 5 Supplement 1, 2018 and is available online at https://doi.org/10.1186/ s40575-018-0061-0. Selected feline abstracts from the conference have been published as Irish Veterinary Journal Volume 71 Supplement 1, 2018 and are available online at https://doi.org/10.1186/s13620-018-0126-0.

and clinical homologies, with comparable subtypes 2 for which a BRAF-MBP gene fusion in one case using RNAseq and are currently for recurrence in the samples, as well as for the presence of this translocation in human glioma cases. Using affected cases and controls of the same breeds, to the identification of somatic alterations by transcriptome analyzes (RNAseq) and exome sequencing (WES) and to carry out genetic linkage and/or genetic association studies (GWAS) to identify genomic regions involved in predisposition. We will also search if and how the artificial selection that led to specific morphological characteristics, such as the shape of the dog ’ s skull (brachycephaly), would have also led to glioma predisposition. improvement in these traits, which is particularly important for HEART – heart conditions are believed to affect as many as 20% of Dobermans, and the symptoms of the disease often appear after a dog has already been used for breeding. Further, significant estimates obtained in the presented analyses indicate validity of the data, thus opening a new window of opportunity for genetic analyses of complex traits in numerically small breeds through the recruitment and collation of data by breed enthusiasts. each dog was measured at the withers. We used linear per allele re- gression to assess the association between ADAMTS17 mutations and height as a continuous variable, and linear regression and log- likelihood ratio tests to assess the shape of the association by comparing a general model with a linear per allele model. The mean heights of affected (n=21), carrier (n=84) and clear (n=122) Petit Basset Griffon Vendeen were 33.41 cm, 34.78 cm and 34.93 cm, respect- ively. The mean heights of affected (n=9), carrier (n=30) and clear (n=26) Shar Pei were 43.32 cm, 47.93 cm and 48.38 cm, respectively. Each breed-specific ADAMTS17 mutation showed a strong association with height in both breeds: Petit Basset Griffon Vendeen (P=7.9 x 10-3); Shar Pei (P=6.9 x 10-5). The shape of the associations ap-peared similar between the two breeds. In humans, ADAMTS17 af- fects skeletal development by modulating the extracellular matrix. A similar mechanism may be present in the dog. We speculate that se- lection for short stature might have inadvertently increased ADAMTS17 mutant allele frequencies and thus increased prevalence of primary open angle glaucoma in these breeds. and Epidemiology 2018, 5(Suppl 2): O5 In domestic dogs, the “ flat-faced ” brachycephalic head shape is a risk factor for developing the respiratory defect, Brachycephalic Obstructive Airway Syndrome (BOAS). As the popularity of breeds such as the French bulldog continues to increase in the UK, so too are the expected incidences of BOAS. For this reason, we be- came interested in the Norwich terrier, a non- brachycephalic breed which presents with Upper Airway Syndrome (UAS), a con- dition highly reminiscent of BOAS. Here, we have studied this single breed to identify genetic association(s) with UAS. Pathological assessments and grading from laryngoscopic examinations held at the Vetsuisse Faculty of the University of Bern, were used as phenotypes in conjunction with microarray genotypes to perform GWAS. In total, 233 Norwich terriers were examined. We identi- fied the same QTL on canine chromosome (CFA) 13 to be associated with the abnormal positioning of laryngeal cartilage and everted saccules in the dogs most severely affected by UAS. We phased genotypes at the CFA13 QTL to conduct haplotype map- ping, which led us to define a 413 kb critical interval which en-compasses a single positional candidate gene. The derived haplotype within this interval is overrepresented: it is found to be homozygous in 61 of 81 (74%) severely affected cases. In con- trast, this homozygous haplotype was identified among 7 of 86 (8.1%) mild/unaffected controls. We have resequenced four dogs representing phenotypic extremes to sixteen-fold depth to identify putatively causal variants. We will provide an update to this ongoing project, which is expected to guide Norwich terrier breeding and inspire additional exploration of the CFA13 locus to improve animal welfare. of multiple transcripts with alternative first exons. of multiple transcripts in the cerebellum through RNA sequencing, RT-PCR of samples from two Buhund cases and dogs of other RT-qPCR analysis and in-silico protein modelling have been used to further investigate the mutation ’ s effect on RNA ex- pression and protein stability. Chronic degenerative diseases (CDGs) are a major welfare concern in canine medicine myxomatous mitral valve disease (MMVD) an For an inher- polygenic and the mechanisms that requires examining molecular events in examination in both temporal and spatial terms changes in gene and pro- tein expression. examined the valvular gene expression at different stages of disease (temporal), different loca- tions (spatial) and in different cell culture models of MMVD. identified as the fundamen- tally important pathway in MMVD initiation and development, and progression to eventual end-stage valve pathology. stringent filtering and quality control, we tested 108,263 SNPs on 42 dogs, comprising 15 cases and 27 controls (call rate ≥ 97%; minor allele frequency ≥ 95%; genotype calls ≥ 90%). Analysis revealed a genome-wide significant association on canine chromosome 33 (-log praw = 2.2 x 10-16) which remained significant after correcting for multiple testing (pgenome = 0.9 x 10-5) and population substructure (p=raw1.6 x 10-17). A 1.3 megabase homozygous disease-associated region was defined, harbouring two candidate genes previously asso- ciated with human retinal degeneration. WGS was undertaken on a single PRA affected LA, and manual inter- rogation of the critical region in identified a long interspersed nu-clear element-1 (LINE-1) insertion, situated within the predicted promotor region of a retinal candidate gene. Due to the position of the LINE-1 insertion, it was not detected in the original WES data of the same case. The LINE-1 insertion was genotyped in 447 dogs across 122 breeds, including 63 LA dogs, and is private to the LA. Seventeen LA dogs (all clinically affected with PRA) were homozygous for the LINE-1 insertions, eight were heterozygous and thirty- eight were homozygous for the wildtype allele. As a result of this study a DNA test for this form of PRA, termed PRA4, has been developed at the Animal Health Trust. To date, 457 LA from 15 countries have been tested for PRA4 (354 UK dogs; car- rier frequency 17%; allele frequency 0.9054). This study highlights the power of utilising several genetic approaches to identify a PRA mutation and develop a diagnostic test to help dog breeders make informed breeding choices, minimising the risk of producing PRA- affected LA dogs. A point mutation in a lincRNA upstream of GDNF is associated with a canine insensitivity to pain: a spontaneous model for human sensory neuropathies. Plos Genetics 2016 Biomedical Variant Database Consortium and the Animal Health Trust Give a Dog a Genome bank) reduced an initial set of > 20 million variants down to a single candidate variant in a novel gene not previously associated with ret- inal degeneration in any species. The candidate variant was genotyped in a total of 1,444 dogs of 175 breeds, 10 cross breed dogs and 3 wolves, with our three PRA-affected Giant Schnauzers being the only homozygotes identified to date. Nine Giant Schnauzer heterozygotes were identified in addition to heterozygotes in three additional breeds of German origin, including the German Giant (Gross) and Medium (Mittel) Spitz and Miniature Longhaired Dachs-hund (MLHD). The genotyping of German Spitz varieties, including 110 Giant Spitz, 21 Medium Spitz, 24 Miniature (Klein) Spitz, 17 Pomeranian (Zwerg) Spitz, and an additional 27 Giant Schnauzers was carried out by collaborators at the University of Bern. We screened a total of 163 MLHD for the candidate variant. Seven German Giant Spitz, one German Medium Spitz and six MLHD heterozygotes were identified, suggesting this may be an ancestral, but rare, mutation. This study highlights the power of using WGS to identify novel genes associated with disease using a very small number of cases. This novel candidate gene, harbouring a variant that is predicted to be the causal mutation of PRA in the Giant Schnauzer, could provide in- sights into gene discoveries in human retinal degenerations. Further functional study options are being explored to confirm the candidate gene ’ s role in retinal function and maintenance. identify the genetic causes or predisposition to canine and human homologous genetic conditions. More recently, the idea emerged that dogs can be of help for therapeutic trials, to screen and validate new drugs in homologous human cancer types. To this aim, we created the canine Cani-DNA biobank in 2003 to col-lect blood and tissue samples from dogs affected with genetic dis- eases and healthy dogs. Cani-DNA contains the native samples and extracted nucleic acids as well as clinical and genealogical data, to distribute samples with high quality controlled procedures. This resource is implemented by a French veterinarian network based on vet practic- es, specialized vet centres and histopathology laborator-ies. In 2012, a contract signed between Cani-DNA and the 4 French vet schools and the Antagene Company allowed a national organization and international visibility. Cani-DNA joined the French consortium of domesticated animals, CRB-Anim (funded by French government 2012-2020), aiming to combine genetic and reproduct- ive resources. To date, Cani-DNA, with its primary site at CNRS Rennes and secondary sites at the fourth Vet Schools and Antagene contains almost 20 000 DNA extracted from blood and 3000 nucleic acids (DNA, RNA) extracted from tissue samples (tumoral and con- trols), representing 300 breeds and over 100 genetic diseases. Samples can be sent to implement Can

Idiopathic or genetic adult-onset epilepsy is a common neurological disorder in domestic dogs. Genetic association has been reported only with ADAM23 on CFA 37 in few breeds. To identify novel epilepsy genes, we performed genome-wide association (GWA) analyses in four new breeds, and investigated the association of the previously reported ADAM23 haplotype with the epilepsy phenotype in eight breeds.

Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), Seattle, WA, MAY 01-05, 2016

In this study, we sought the genetic cause of self-mutilation syndrome in sporting dogs, which corresponds to human Hereditary Sensory and Autonomic Neuropathies (HSAN). We have identified a genetic mutation upstream of the gene encoding Glial cell line-Derived Neurotrophic Factor (GDNF). This mutation is responsible for insensitivity to pain in four sporting dog breeds and it perfectly segregates with the disease in 250 sporting dogs of known clinical status. Moreover, it was not found in any of the 900 unaffected dogs from 130 different breeds. Since this mutation is localized in a long non-coding RNA, we performed an in-depth analysis of the genomic region (locus) as well as gene expression analyses to understand its role in the pathophysiology of the disease. Thus, in addition to the discovery of a novel candidate gene for HSAN in humans, we propose a transcriptional regulation mechanism based on a “partnership” between GDNF and a long non-coding RNA (lncRNA).

Dogs have a great sense of olfaction, but unlike many other mammals, which also show superior olfactory performance, many dog breeds have been created for hunting purposes for which olfactory performance is particularly important. In this article, we review the dog genetic characteristics that could make dogs so gifted with respect to olfactory ability. We also present some preliminary results on RNA profiling analyses of dog olfactory epithelium and show that the level of olfactory receptor expression per olfactory neuron might be higher in dogs than in rats.