Publications by authors named "Maud Rimbault"

18 Publications

  • Page 1 of 1

Donskoy cats as a new model of oculocutaneous albinism with the identification of a splice-site variant in Hermansky-Pudlak Syndrome 5 gene.

Pigment Cell Melanoma Res 2020 11 29;33(6):814-825. Epub 2020 Jun 29.

Univ Lyon, VetAgro Sup, Marcy l'Etoile, France.

In the feline Donskoy breed, a phenotype that breeders call "pink-eye," with associated light-brown skin, yellow irises and red-eye effect, has been described. Genealogical data indicated an autosomal recessive inheritance pattern. A single candidate region was identified by genome-wide association study and SNP-based homozygosity mapping. Within that region, we further identified HPS5 (HPS5 Biogenesis Of Lysosomal Organelles Complex 2 Subunit 2) as a strong candidate gene, since HPS5 variants have been identified in humans and animals with Hermansky-Pudlak syndrome 5 or oculocutaneous albinism. A homozygous c.2571-1G>A acceptor splice-site variant located in intron 16 of HPS5 was identified in pink-eye cats. Segregation of the variant was 100% consistent with the inheritance pattern. Genotyping of 170 cats from 19 breeds failed to identify a single carrier in non-Donskoy cats. The c.2571-1G>A variant leads to HPS5 exon-16 splicing that is predicted to produce a 52 amino acids in-frame deletion in the protein. These results support an association of the pink-eye phenotype with the c.2571-1G>A variant. The pink-eye Donskoy cat extends the panel of reported HPS5 variants and offers an opportunity for in-depth exploration of the phenotypic consequences of a new HPS5 variant.
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http://dx.doi.org/10.1111/pcmr.12906DOI Listing
November 2020

Identification of a Missense Variant in Involved in Dilution of Phaeomelanin Leading to White or Cream Coat Color in Dogs.

Genes (Basel) 2019 05 21;10(5). Epub 2019 May 21.

Institut de Génétique et Développement de Rennes, CNRS-UMR6290, Université de Rennes1, 35000 Rennes, France.

White coat color in mammals has been selected several times during the domestication process. Numerous dog breeds are fixed for one form of white coat color that involves darkly pigmented skin. The genetic basis of this color, due to the absence of pigment in the hairs, was suggested to correspond to extreme dilution of the phaeomelanin, by both the expression of only phaeomelanin (locus E) and its extreme dilution (locus I). To go further, we performed genome-wide association studies (GWAS) using a multiple breed approach. The first GWAS, using 34 white dogs and 128 non-white dogs, including White Shepherds, Poodles, Cotons de Tulear and Bichons allowed us to identify two significantly associated loci on the locus E and a novel locus on chromosome 20. A second GWAS using 15 other breeds presenting extreme phaeomelanin dilution confirmed the position of locus I on the chromosome 20 (position 55 Mb = 6 × 10). Using whole-genome sequencing, we identified a missense variant in the first exon of , a gene recently identified to be involved in human, mouse and horse pigmentation. We confirmed the role of this variant in phaeomelanin dilution of numerous canine breeds, and the conserved role of in mammalian pigmentation.
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http://dx.doi.org/10.3390/genes10050386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562630PMC
May 2019

Genomic Analyses Reveal the Influence of Geographic Origin, Migration, and Hybridization on Modern Dog Breed Development.

Cell Rep 2017 04;19(4):697-708

Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:

There are nearly 400 modern domestic dog breeds with a unique histories and genetic profiles. To track the genetic signatures of breed development, we have assembled the most diverse dataset of dog breeds, reflecting their extensive phenotypic variation and heritage. Combining genetic distance, migration, and genome-wide haplotype sharing analyses, we uncover geographic patterns of development and independent origins of common traits. Our analyses reveal the hybrid history of breeds and elucidate the effects of immigration, revealing for the first time a suggestion of New World dog within some modern breeds. Finally, we used cladistics and haplotype sharing to show that some common traits have arisen more than once in the history of the dog. These analyses characterize the complexities of breed development, resolving longstanding questions regarding individual breed origination, the effect of migration on geographically distinct breeds, and, by inference, transfer of trait and disease alleles among dog breeds.
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http://dx.doi.org/10.1016/j.celrep.2017.03.079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5492993PMC
April 2017

Analysis of large versus small dogs reveals three genes on the canine X chromosome associated with body weight, muscling and back fat thickness.

PLoS Genet 2017 Mar 3;13(3):e1006661. Epub 2017 Mar 3.

Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America.

Domestic dog breeds display significant diversity in both body mass and skeletal size, resulting from intensive selective pressure during the formation and maintenance of modern breeds. While previous studies focused on the identification of alleles that contribute to small skeletal size, little is known about the underlying genetics controlling large size. We first performed a genome-wide association study (GWAS) using the Illumina Canine HD 170,000 single nucleotide polymorphism (SNP) array which compared 165 large-breed dogs from 19 breeds (defined as having a Standard Breed Weight (SBW) >41 kg [90 lb]) to 690 dogs from 69 small breeds (SBW ≤41 kg). We identified two loci on the canine X chromosome that were strongly associated with large body size at 82-84 megabases (Mb) and 101-104 Mb. Analyses of whole genome sequencing (WGS) data from 163 dogs revealed two indels in the Insulin Receptor Substrate 4 (IRS4) gene at 82.2 Mb and two additional mutations, one SNP and one deletion of a single codon, in Immunoglobulin Superfamily member 1 gene (IGSF1) at 102.3 Mb. IRS4 and IGSF1 are members of the GH/IGF1 and thyroid pathways whose roles include determination of body size. We also found one highly associated SNP in the 5'UTR of Acyl-CoA Synthetase Long-chain family member 4 (ACSL4) at 82.9 Mb, a gene which controls the traits of muscling and back fat thickness. We show by analysis of sequencing data from 26 wolves and 959 dogs representing 102 domestic dog breeds that skeletal size and body mass in large dog breeds are strongly associated with variants within IRS4, ACSL4 and IGSF1.
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http://dx.doi.org/10.1371/journal.pgen.1006661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357063PMC
March 2017

Whole-genome sequence, SNP chips and pedigree structure: building demographic profiles in domestic dog breeds to optimize genetic-trait mapping.

Dis Model Mech 2016 12 17;9(12):1445-1460. Epub 2016 Nov 17.

Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA

In the decade following publication of the draft genome sequence of the domestic dog, extraordinary advances with application to several fields have been credited to the canine genetic system. Taking advantage of closed breeding populations and the subsequent selection for aesthetic and behavioral characteristics, researchers have leveraged the dog as an effective natural model for the study of complex traits, such as disease susceptibility, behavior and morphology, generating unique contributions to human health and biology. When designing genetic studies using purebred dogs, it is essential to consider the unique demography of each population, including estimation of effective population size and timing of population bottlenecks. The analytical design approach for genome-wide association studies (GWAS) and analysis of whole-genome sequence (WGS) experiments are inextricable from demographic data. We have performed a comprehensive study of genomic homozygosity, using high-depth WGS data for 90 individuals, and Illumina HD SNP data from 800 individuals representing 80 breeds. These data were coupled with extensive pedigree data analyses for 11 breeds that, together, allowed us to compute breed structure, demography, and molecular measures of genome diversity. Our comparative analyses characterize the extent, formation and implication of breed-specific diversity as it relates to population structure. These data demonstrate the relationship between breed-specific genome dynamics and population architecture, and provide important considerations influencing the technological and cohort design of association and other genomic studies.
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http://dx.doi.org/10.1242/dmm.027037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5200897PMC
December 2016

Comparison against 186 canid whole-genome sequences reveals survival strategies of an ancient clonally transmissible canine tumor.

Genome Res 2015 Nov 31;25(11):1646-55. Epub 2015 Jul 31.

Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA;

Canine transmissible venereal tumor (CTVT) is a parasitic cancer clone that has propagated for thousands of years via sexual transfer of malignant cells. Little is understood about the mechanisms that converted an ancient tumor into the world's oldest known continuously propagating somatic cell lineage. We created the largest existing catalog of canine genome-wide variation and compared it against two CTVT genome sequences, thereby separating alleles derived from the founder's genome from somatic mutations that must drive clonal transmissibility. We show that CTVT has undergone continuous adaptation to its transmissible allograft niche, with overlapping mutations at every step of immunosurveillance, particularly self-antigen presentation and apoptosis. We also identified chronologically early somatic mutations in oncogenesis- and immune-related genes that may represent key initiators of clonal transmissibility. Thus, we provide the first insights into the specific genomic aberrations that underlie CTVT's dogged perseverance in canids around the world.
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http://dx.doi.org/10.1101/gr.190314.115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617961PMC
November 2015

Derived variants at six genes explain nearly half of size reduction in dog breeds.

Genome Res 2013 Dec 11;23(12):1985-95. Epub 2013 Sep 11.

Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA;

Selective breeding of dogs by humans has generated extraordinary diversity in body size. A number of multibreed analyses have been undertaken to identify the genetic basis of this diversity. We analyzed four loci discovered in a previous genome-wide association study that used 60,968 SNPs to identify size-associated genomic intervals, which were too large to assign causative roles to genes. First, we performed fine-mapping to define critical intervals that included the candidate genes GHR, HMGA2, SMAD2, and STC2, identifying five highly associated markers at the four loci. We hypothesize that three of the variants are likely to be causative. We then genotyped each marker, together with previously reported size-associated variants in the IGF1 and IGF1R genes, on a panel of 500 domestic dogs from 93 breeds, and identified the ancestral allele by genotyping the same markers on 30 wild canids. We observed that the derived alleles at all markers correlated with reduced body size, and smaller dogs are more likely to carry derived alleles at multiple markers. However, breeds are not generally fixed at all markers; multiple combinations of genotypes are found within most breeds. Finally, we show that 46%-52.5% of the variance in body size of dog breeds can be explained by seven markers in proximity to exceptional candidate genes. Among breeds with standard weights <41 kg (90 lb), the genotypes accounted for 64.3% of variance in weight. This work advances our understanding of mammalian growth by describing genetic contributions to canine size determination in non-giant dog breeds.
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http://dx.doi.org/10.1101/gr.157339.113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847769PMC
December 2013

The insulin-like growth factor 1 receptor (IGF1R) contributes to reduced size in dogs.

Mamm Genome 2012 Dec 18;23(11-12):780-90. Epub 2012 Aug 18.

Department of Biology, Colgate University, 13 Oak Drive, Hamilton, NY 13346, USA.

Domestic dog breeds have undergone intense selection for a variety of morphologic features, including size. Among small-dog breeds, defined as those averaging less than ~15 in. at the withers, there remains still considerable variation in body size. Yet essentially all such dogs are fixed for the same allele at the insulin-like growth factor 1 gene, which we and others previously found to be a size locus of large effect. In this study we sought to identify additional genes that contribute to tiny size in dogs using an association scan with the single nucleotide polymorphism (SNP) dataset CanMap, in which 915 purebred dogs were genotyped at 60,968 SNP markers. Our strongest association for tiny size (defined as breed-average height not more than 10 in. at the withers) was on canine chromosome 3 (p = 1.9 × 10(-70)). Fine mapping revealed a nonsynonymous SNP at chr3:44,706,389 that changes a highly conserved arginine at amino acid 204 to histidine in the insulin-like growth factor 1 receptor (IGF1R). This mutation is predicted to prevent formation of several hydrogen bonds within the cysteine-rich domain of the receptor's ligand-binding extracellular subunit. Nine of 13 tiny dog breeds carry the mutation and many dogs are homozygous for it. This work underscores the central importance of the IGF1 pathway in controlling the tremendous size diversity of dogs.
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http://dx.doi.org/10.1007/s00335-012-9417-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511640PMC
December 2012

So many doggone traits: mapping genetics of multiple phenotypes in the domestic dog.

Hum Mol Genet 2012 Oct 9;21(R1):R52-7. Epub 2012 Aug 9.

National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.

The worldwide dog population is fragmented into >350 domestic breeds. Breeds share a common ancestor, the gray wolf. The intense artificial selection imposed by humans to develop breeds with particular behaviors and phenotypic traits has occurred primarily in the last 200-300 years. As a result, the number of genes controlling the major differences in body size, leg length, head shape, etc. that define each dog is small, and genetically tractable. This is in comparison to many human complex traits where small amounts of variance are controlled by literally hundreds of genes. We have been interested in disentangling the genetic mechanisms controlling breed-defining morphological traits in the domestic dog. The structure of the dog population, comprised large numbers of pure breeding populations, makes this task surprisingly doable. In this review, we summarize recent work on the genetics of body size, leg length and skull shape, while setting the stage for tackling other traits. It is our expectation that these results will contribute to a better understanding of mammalian developmental processes overall.
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http://dx.doi.org/10.1093/hmg/dds323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459646PMC
October 2012

Variation of BMP3 contributes to dog breed skull diversity.

PLoS Genet 2012 2;8(8):e1002849. Epub 2012 Aug 2.

Cancer Genetics Branch, National Human Genome Research Institute, Bethesda, Maryland, United States of America.

Since the beginnings of domestication, the craniofacial architecture of the domestic dog has morphed and radiated to human whims. By beginning to define the genetic underpinnings of breed skull shapes, we can elucidate mechanisms of morphological diversification while presenting a framework for understanding human cephalic disorders. Using intrabreed association mapping with museum specimen measurements, we show that skull shape is regulated by at least five quantitative trait loci (QTLs). Our detailed analysis using whole-genome sequencing uncovers a missense mutation in BMP3. Validation studies in zebrafish show that Bmp3 function in cranial development is ancient. Our study reveals the causal variant for a canine QTL contributing to a major morphologic trait.
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http://dx.doi.org/10.1371/journal.pgen.1002849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410846PMC
December 2012

The MTAP-CDKN2A locus confers susceptibility to a naturally occurring canine cancer.

Cancer Epidemiol Biomarkers Prev 2012 Jul 23;21(7):1019-27. Epub 2012 May 23.

Cancer Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.

Background: Advantages offered by canine population substructure, combined with clinical presentations similar to human disorders, makes the dog an attractive system for studies of cancer genetics. Cancers that have been difficult to study in human families or populations are of particular interest. Histiocytic sarcoma is a rare and poorly understood neoplasm in humans that occurs in 15% to 25% of Bernese Mountain Dogs (BMD).

Methods: Genomic DNA was collected from affected and unaffected BMD in North America and Europe. Both independent and combined genome-wide association studies (GWAS) were used to identify cancer-associated loci. Fine mapping and sequencing narrowed the primary locus to a single gene region.

Results: Both populations shared the same primary locus, which features a single haplotype spanning MTAP and part of CDKN2A and is present in 96% of affected BMD. The haplotype is within the region homologous to human chromosome 9p21, which has been implicated in several types of cancer.

Conclusions: We present the first GWAS for histiocytic sarcoma in any species. The data identify an associated haplotype in the highly cited tumor suppressor locus near CDKN2A. These data show the power of studying distinctive malignancies in highly predisposed dog breeds.

Impact: Here, we establish a naturally occurring model of cancer susceptibility due to CDKN2 dysregulation, thus providing insight about this cancer-associated, complex, and poorly understood genomic region.
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http://dx.doi.org/10.1158/1055-9965.EPI-12-0190-TDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392365PMC
July 2012

Breed-specific ancestry studies and genome-wide association analysis highlight an association between the MYH9 gene and heat tolerance in Alaskan sprint racing sled dogs.

Mamm Genome 2012 Feb 22;23(1-2):178-94. Epub 2011 Nov 22.

Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 50 South Drive, Building 50, Room 5351, Bethesda, MD 20892, USA.

Alaskan sled dogs are a genetically distinct population shaped by generations of selective interbreeding with purebred dogs to create a group of high-performance athletes. As a result of selective breeding strategies, sled dogs present a unique opportunity to employ admixture-mapping techniques to investigate how breed composition and trait selection impact genomic structure. We used admixture mapping to investigate genetic ancestry across the genomes of two classes of sled dogs, sprint and long-distance racers, and combined that with genome-wide association studies (GWAS) to identify regions that correlate with performance-enhancing traits. The sled dog genome is enhanced by differential contributions from four non-admixed breeds (Alaskan Malamute, Siberian Husky, German Shorthaired Pointer, and Borzoi). A principal components analysis (PCA) of 115,000 genome-wide SNPs clearly resolved the sprint and distance populations as distinct genetic groups, with longer blocks of linkage disequilibrium (LD) observed in the distance versus sprint dogs (7.5-10 and 2.5-3.75 kb, respectively). Furthermore, we identified eight regions with the genomic signal from either a selective sweep or an association analysis, corroborated by an excess of ancestry when comparing sprint and distance dogs. A comparison of elite and poor-performing sled dogs identified a single region significantly associated with heat tolerance. Within the region we identified seven SNPs within the myosin heavy chain 9 gene (MYH9) that were significantly associated with heat tolerance in sprint dogs, two of which correspond to conserved promoter and enhancer regions in the human ortholog.
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http://dx.doi.org/10.1007/s00335-011-9374-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3320045PMC
February 2012

Genetics of canine olfaction and receptor diversity.

Mamm Genome 2012 Feb 13;23(1-2):132-43. Epub 2011 Nov 13.

Institut de Génétique et Développement de Rennes, UMR6061 CNRS Université de Rennes 1, Faculté de Médecine, 2 avenue Prof. Léon Bernard, CS34317, 35043 Rennes Cedex, France.

Olfaction is a particularly important sense in the dog. Humans selected for this capacity during the domestication process, and selection has continued to be employed to enhance this ability. In this review we first describe the different olfactory systems that exist and the different odorant receptors that are expressed in those systems. We then focus on the dog olfactory receptors by describing the olfactory receptor gene repertoire and its polymorphisms. Finally, we discuss the different uses of dog olfaction and the questions that still need to be studied.
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http://dx.doi.org/10.1007/s00335-011-9371-1DOI Listing
February 2012

cAMP and IP3 signaling pathways in HEK293 cells transfected with canine olfactory receptor genes.

J Hered 2011 Sep-Oct;102 Suppl 1:S47-61

Institute of Genetic and Development of Rennes, CNRS Unité de Recherche Mixte 6061, Faculté de Médecine, Rennes, F-35043 France.

Olfactory receptors (ORs) expressed at the cell surface of olfactory sensory neurons lining the olfactory epithelium are the first actors of events leading to odor perception and recognition. As for other mammalian ORs, few dog OR have been deorphanized, mainly because of the absence of good methodology and the difficulties encountered to express ORs at the cell surface. Within this work, our aim was 1) to deorphanize a large subset of dog OR and 2) to compare the implication of the 2 main pathways, namely the cAMP and inositol 1,4,5-triphosphate (IP3) pathways, in the transduction of the olfactory message. For this, we used 2 independent tests to assess the importance of each of these 2 pathways and analyzed the responses of 47 canine family 6 ORs to a number of aliphatic compounds. We found these ORs globally capable of inducing intracellular calcium elevation through the IP3 pathway as confirmed by the use of specific inhibitors and/or a cAMP increase in response to aldehyde exposure. We showed that the implication of the cAMP or/and IP3 pathway was dependent upon the ligand-receptor combination rather than on one or the other partner. Finally, by exposing OR-expressing cells to the 21 possible pairs of C6-C12 aliphatic aldehydes, we confirmed that some odorant pairs may have an inhibitory or additive effect. Altogether, these results reinforce the notion that odorant receptor subfamilies may constitute functional units and call for a more systematic use of 2 complementary tests interrogating the cAMP and IP3 pathways when deorphanizing ORs.
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http://dx.doi.org/10.1093/jhered/esr033DOI Listing
December 2011

RNA profiles of rat olfactory epithelia: individual and age related variations.

BMC Genomics 2009 Dec 2;10:572. Epub 2009 Dec 2.

Faculté de Médecine, Université de Rennes 1, Institut de Génétique et Développement de Rennes, UEB, Rennes, France.

Background: Mammalian genomes contain a large number (approximately 1000) of olfactory receptor (OR) genes, many of which (20 to 50%) are pseudogenes. OR gene transcription is not restricted to the olfactory epithelium, but is found in numerous tissues. Using microarray hybridization and RTqPCR, we analyzed the mRNA profiles of the olfactory epithelium of male and female Brown Norway rats of different origins and ages (newborn, adult and old).

Results: (1) We observed very little difference between males and females and between rats from two different suppliers. (2) Different OR genes were expressed at varying levels, rather than uniformly across the four endoturbinates. (3) A large proportion of the gene transcripts (2/3 of all probes) were detected in all three age groups. Adult and older rats expressed similar numbers of OR genes, both expressing more OR genes than newborns. (4) Comparisons of whole transcriptomes or transcription profiles of expressed OR genes only showed a clear clustering of the samples as a function of age. (5) Most OR genes were expressed at lower levels at birth than in older animals, but a small number of OR genes were expressed specifically or were overexpressed in newborns.

Conclusion: Not all OR genes are expressed at a detectable level. Pups expressed fewer OR genes than adult rats, and generally at a lower level; however, a small subset of OR genes were more strongly expressed in these newborn rats. The reasons for these differences are not understood. However, the specific expression of some OR genes in newborn olfactory epithelia may be related to the blindness and deafness of pups at birth, when these pups are heavily reliant on olfaction and their mother.
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http://dx.doi.org/10.1186/1471-2164-10-572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797534PMC
December 2009

Genetic diversity of canine olfactory receptors.

BMC Genomics 2009 Jan 14;10:21. Epub 2009 Jan 14.

Institut de Génétique et Développement de Rennes, CNRS UMR 6061, Université de Rennes 1, 2 Avenue du Professeur Léon Bernard, 43 Rennes, France.

Background: Evolution has resulted in large repertoires of olfactory receptor (OR) genes, forming the largest gene families in mammalian genomes. Knowledge of the genetic diversity of olfactory receptors is essential if we are to understand the differences in olfactory sensory capability between individuals. Canine breeds constitute an attractive model system for such investigations.

Results: We sequenced 109 OR genes considered representative of the whole OR canine repertoire, which consists of more than 800 genes, in a cohort of 48 dogs of six different breeds. SNP frequency showed the overall level of polymorphism to be high. However, the distribution of SNP was highly heterogeneous among OR genes. More than 50% of OR genes were found to harbour a large number of SNP, whereas the rest were devoid of SNP or only slightly polymorphic. Heterogeneity was also observed across breeds, with 25% of the SNP breed-specific. Linkage disequilibrium within OR genes and OR clusters suggested a gene conversion process, consistent with a mean level of polymorphism higher than that observed for introns and intergenic sequences. A large proportion (47%) of SNP induced amino-acid changes and the Ka/Ks ratio calculated for all alleles with a complete ORF indicated a low selective constraint with respect to the high level of redundancy of the olfactory combinatory code and an ongoing pseudogenisation process, which affects dog breeds differently.

Conclusion: Our demonstration of a high overall level of polymorphism, likely to modify the ligand-binding capacity of receptors distributed differently within the six breeds tested, is the first step towards understanding why Labrador Retrievers and German Shepherd Dogs have a much greater potential for use as sniffer dogs than Pekingese dogs or Greyhounds. Furthermore, the heterogeneity in OR polymorphism observed raises questions as to why, in a context in which most OR genes are highly polymorphic, a subset of these genes is not? This phenomenon may be related to the nature of their ligands and their importance in everyday life.
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http://dx.doi.org/10.1186/1471-2164-10-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2635374PMC
January 2009

Olfactory receptor sequence polymorphism within and between breeds of dogs.

J Hered 2005 26;96(7):812-6. Epub 2005 Oct 26.

UMR 6061,Génétique et Développement CNRS-Université de Rennes 1, France.

Olfactory receptors, to which odorant molecules specifically bind, are encoded by the largest gene family yet identified in the mammalian genome. We investigated additional polymorphism due to the possible existence of multiple alleles dispersed in different dog breeds by carrying out a survey of the sequences of 16 olfactory receptor genes in a sample of 95 dogs of 20 different breeds. The level of polymorphism was high--all genes were found to have allelic variants--leading to amino acid changes and pseudogenization of some alleles in a number of cases. This preliminary study also revealed that some alleles are breed specific (or rare in the dog population), with some representing the major allele in the breeds concerned.
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http://dx.doi.org/10.1093/jhered/esi113DOI Listing
October 2006

The dog and rat olfactory receptor repertoires.

Genome Biol 2005 28;6(10):R83. Epub 2005 Sep 28.

UMR 6061, Génétique et Développement CNRS-Université de Rennes 1, 35043 Rennes Cedex, France.

Background: Dogs and rats have a highly developed capability to detect and identify odorant molecules, even at minute concentrations. Previous analyses have shown that the olfactory receptors (ORs) that specifically bind odorant molecules are encoded by the largest gene family sequenced in mammals so far.

Results: We identified five amino acid patterns characteristic of ORs in the recently sequenced boxer dog and brown Norway rat genomes. Using these patterns, we retrieved 1,094 dog genes and 1,493 rat genes from these shotgun sequences. The retrieved sequences constitute the olfactory receptor repertoires of these two animals. Subsets of 20.3% (for the dog) and 19.5% (for the rat) of these genes were annotated as pseudogenes as they had one or several mutations interrupting their open reading frames. We performed phylogenetic studies and organized these two repertoires into classes, families and subfamilies.

Conclusion: We have established a complete or almost complete list of OR genes in the dog and the rat and have compared the sequences of these genes within and between the two species. Our results provide insight into the evolutionary development of these genes and the local amplifications that have led to the specific amplification of many subfamilies. We have also compared the human and rat ORs with the human and mouse OR repertoires.
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http://dx.doi.org/10.1186/gb-2005-6-10-r83DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1257466PMC
December 2006