Genetic diversity of canine olfactory receptors

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p

The dog and rat olfactory receptor repertoires

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

Складова духовної культури та запорука стабільності політичного режиму Марокко

Головною тенденцією останніх десятиліть стали процеси глобалізації, які по-різному впливають на країни, так би мовити, „старого центру” та „периферії”. У „центрі” зосередились країни, в яких демократія має давні традиції, що зміцнювалися на засадах західноєвропейської християнської культури. Якщо взяти африканський континент, то побачимо там сукупність специфічних проблем, які одночасно наближають і віддаляють країни, що її складають, від глобалізаційних процесів. Отже, природно, що увага спеціалістів з проблем світового демократичного транзиту, культурології, політології, хоча й з різних причин, прикута до „чорного континенту”. Однією з проблем, що викликає небуденний інтерес дослідників, є стосунки, взаємодія західної та східної цивілізацій

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

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

SuperB: next-generation e+e- B-factory collider

International audienceThe SuperB international team continues to optimize the design of an electron-positron collider, which will allow the enhanced study of the origins of flavor physics. The project combines the best features of a linear collider (high single- collision luminosity) and a storage-ring collider (high rep- etition rate), bringing together all accelerator physics as- pects to make a very high luminosity of 10^36 cm^−2 sec^−1 . This asymmetric-energy collider with a polarized electron beam will produce hundreds of millions of B-mesons at the Υ(4S) resonance. The present design is based on ex- tremely low emittance beams colliding at a large Piwin- ski angle to allow very low β⋆y without the need for ultra short bunches. Use of crab-waist sextupoles will enhance the luminosity, suppressing dangerous resonances and al- lowing for a higher beam-beam parameter. The project has flexible beam parameters, improved dynamic aperture, and spin-rotators in the Low Energy Ring for longitudinal po- larization of the electron beam at the Interaction Point. Op- timized for best colliding-beam performance, the facility may also provide high-brightness photon beams for syn- chrotron radiation applications

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

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 drivers of 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

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

International audienceDomestic 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

Variation of BMP3 Contributes to Dog Breed Skull Diversity

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

Analyses génomiques et fonctionnelles des récepteurs olfactifs du chien et du rat

L'olfaction est l'un des sens développés par les animaux pour communiquer entre eux, rechercher leur nourriture ou éviter les dangers du monde extérieur. La détection et la reconnaissance d'une molécule odorante sont des processus complexes qui requièrent la liaison spécifique de la molécule odorante à des récepteurs spécialisés, les récepteurs olfactifs (OR). Nous avons identifié les répertoires des gènes OR de chien et de rat par analyse bioinformatique des données de séquençage de leurs génomes et analysé le polymorphisme d une centaine de gènes OR dans une cohorte de 48 chiens de six races différentes. Cette étude révèle un grand taux de polymorphisme général mais variable selon les gènes avec des spécificités propres à chaque race. Nous avons également analysé par hybridation sur puces le transcriptome de l épithelium olfactif de rat et montré que ce dernier varie légèrement en fonction de l age et de l environnement olfactif auquel les rats sont soumis.Olfaction is a complicated physiological function on which all animals relay heavily to sense the outside world in order to find sexual partners, food and avoid predators. Detection of odorants is first dependant upon the binding of the odorant molecules to specific receptors, named olfactory receptors (OR). Upon the binding of an odorant molecule signals are sent to different brain areas. OR are expressed at the surface of the cilia of the olfactory epithelium. We have identified by mining the dog and rat genome sequences the two complete OR gene repertoires. We have studied by re-sequencing a large number of OR genes within a cohort of 48 dogs representing six breeds and shown that most of them are highly polymorphic. We have also analyzed by microarray hybridization the transcriptome of rat olfactory epithelia and shown it varies slightly upon age and the odorant environment.RENNES1-BU Sciences Philo (352382102) / SudocSudocFranceF