Population structure and genetic history of Tibetan Terriers

International audienceAbstractBackgroundTibetan Terrier is a popular medium-sized companion dog breed. According to the history of the breed, the western population of Tibetan Terriers includes two lineages, Lamleh and Luneville. These two lineages derive from a small number of founder animals from the native Tibetan Terrier population, which were brought to Europe in the 1920s. For almost a century, the western population of Tibetan Terriers and the native population in Tibet were reproductively isolated. In this study, we analysed the structure of the western population of Tibetan Terriers, the original native population from Tibet and of different crosses between these two populations. We also examined the genetic relationships of Tibetan Terriers with other dog breeds, especially terriers and some Asian breeds, and the within-breed structure of both Tibetan Terrier populations.ResultsOur analyses were based on high-density single nucleotide polymorphism (SNP) array (Illumina HD Canine 170 K) and microsatellite (18 loci) genotypes of 64 Tibetan Terriers belonging to different populations and lineages. For the comparative analysis, we used 348 publicly available SNP array genotypes of dogs from other breeds. We found that the western population of Tibetan Terriers and the native Tibetan Terriers clustered together with other Asian dog breeds, whereas all other terrier breeds were grouped into a separate group. We were also able to differentiate the western Tibetan Terrier lineages (Lamleh and Luneville) from the native Tibetan Terrier population.ConclusionsOur results reveal the relationships between the western and native populations of Tibetan Terriers and support the hypothesis that Tibetan Terrier belongs to the group of ancient dog breeds of Asian origin, which are close to the ancestors of the modern dog that were involved in the early domestication process. Thus, we were able to reject the initial hypothesis that Tibetan Terriers belong to the group of terrier breeds. The existence of this native population of Tibetan Terriers at its original location represents an exceptional and valuable genetic resource

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

Universal DNA methylation age across mammalian tissues

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.Publisher PDFPeer reviewe

Universal DNA methylation age across mammalian tissues.

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals

Formaldehyde removal by photocatalytic mortar mixed with TiO2.

internationa

Characterization and photocatalytic performance in air of cementitious materials containing TiO2. Case study of formaldehyde removal

AIR:EAU+EPU:JMH:CG

Photocatalytic oxidation of VOCs by cementitious materials mixed with TiO2

internationa

UN MODÈLE SPONTANÉ CANIN DE NEUROPATHIE SENSORIELLE HUMAINE : IDENTIFICATION D’UNE MUTATION EN AMONT D’UN FACTEUR NEUROTROPHIQUE

International audienceIn 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).Dans cette étude, nous avons recherché la cause génétique du syndrome d’automutilation chez les chiens de chasse, qui correspond chez l’Homme à une neuropathie sensitive de type HSAN. Nous avons identifié une mutation en amont d’un gène codant un facteur neurotrophique : GDNF (« Glial cell line-Derived Neurotrophic Factor »). Cette mutation ségrége parfaitement avec la maladie chez 250 chiens de chasse de statut clinique connu et est absente chez 900 chiens indemnes de 130 autres races. Cette mutation étant située dans un ARN long non codant, une analyse fine de la région chromosomique et des études d’expression de gènes ont été réalisées pour comprendre son rôle dans la physiopathologie de la maladie. Ainsi, non seulement, nous apportons un nouveau gène candidat pour les neuropathies humaines, mais nous proposons également un mécanisme de régulation transcriptionnelle original, basé sur un « partenariat » entre le gène codant le facteur neurotrophique et l’ARN long non codant

Conservation of <i>IGSF1</i> mutated codons (in bold) between mammals.

<p>Conservation of <i>IGSF1</i> mutated codons (in bold) between mammals.</p

Derived allele frequencies at multiple loci involved in body weight and size variations in (A) modern dog breeds, (B) modern dog breeds without inclusion of muscled breeds, (C) only muscled breeds.

<p>The frequency of the derived allele in 5-kg weigh classes is represented on a color scale. Dogs with a SBW above 65 kg are collapsed in a single category (>65 kg) due to the lack of genotype variation in the group at these markers. Muscled breeds include the Boston Terrier (BOST), French Bulldog (FBUL), Miniature Bull Terrier (MBLT), Staffordshire Bull Terrier (STAF), Chinese Shar-pei (SHAR), Bulldog (BULD), Chow-Chow (CHOW), American Staffordshire Terrier (AMST), Boxer (BOX), Beauceron (BEAU), Bullmastiff (BULM), Bernese Mountain Dog (BMD), Rottweiler (ROTT), Leonberger (LEON), Tibetan Mastiff (TIBM), Neapolitan Mastiff (NEAM), Newfoundland (NEWF), Dogue de Bordeaux DDBX), English Mastiff (MAST) and Saint Bernard (STBD).</p