PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (262399)

Clipboard (0)
None

Related Articles

1.  Chromosomal Mapping of Canine-Derived BAC Clones to the Red Fox and American Mink Genomes 
Journal of Heredity  2009;100(Suppl 1):S42-S53.
High-quality sequencing of the dog (Canis lupus familiaris) genome has enabled enormous progress in genetic mapping of canine phenotypic variation. The red fox (Vulpes vulpes), another canid species, also exhibits a wide range of variation in coat color, morphology, and behavior. Although the fox genome has not yet been sequenced, canine genomic resources have been used to construct a meiotic linkage map of the red fox genome and begin genetic mapping in foxes. However, a more detailed gene-specific comparative map between the dog and fox genomes is required to establish gene order within homologous regions of dog and fox chromosomes and to refine breakpoints between homologous chromosomes of the 2 species. In the current study, we tested whether canine-derived gene–containing bacterial artificial chromosome (BAC) clones can be routinely used to build a gene-specific map of the red fox genome. Forty canine BAC clones were mapped to the red fox genome by fluorescence in situ hybridization (FISH). Each clone was uniquely assigned to a single fox chromosome, and the locations of 38 clones agreed with cytogenetic predictions. These results clearly demonstrate the utility of FISH mapping for construction of a whole-genome gene-specific map of the red fox. The further possibility of using canine BAC clones to map genes in the American mink (Mustela vison) genome was also explored. Much lower success was obtained for this more distantly related farm-bred species, although a few BAC clones were mapped to the predicted chromosomal locations.
doi:10.1093/jhered/esp037
PMCID: PMC3139363  PMID: 19546120
Canis lupus familiaris; comparative genomics; FISH; Mustela vison; Vulpes vulpes
2.  Animal evolution during domestication: the domesticated fox as a model 
Summary
We review the evolution of domestic animals, emphasizing the effect of the earliest steps of domestication on its course. Using the first domesticated species, the dog (Canis familiaris) as an illustration, we describe the evolutionary specificities of the historical domestication, such as the high level and wide range of diversity. We suggest that the process of earliest domestication via unconscious and later conscious selection of human-defined behavioral traits may accelerate phenotypic variations. The review is based on the results of the long-term experiment designed to reproduce early mammalian domestication in the silver fox (Vulpes vulpes) selected for tameability, or amenability to domestication. We describe changes in behavior, morphology and physiology that appeared in the fox during its selection for tameability and that were similar to those observed in the domestic dog. Based on the experimental fox data and survey of relevant data, we discuss the developmental, genetic and possible molecular-genetic mechanisms of these changes. We assign the causative role in evolutionary transformation of domestic animals to selection for behavior and to the neurospecific regulatory genes it affects.
doi:10.1002/bies.200800070
PMCID: PMC2763232  PMID: 19260016
3.  Directional Asymmetry in the Limbs, Skull and Pelvis of the Silver Fox (V. vulpes) 
Journal of morphology  2010;271(12):1501-1508.
Directional asymmetry (DA) is a characteristic of most vertebrates, most strikingly exhibited by the placement of various organs (heart, lungs, liver, etc.) but also noted in small differences in the metrics of skeletal structures such as the pelvis of certain fish or sauropsids. We have analyzed DA in the skeleton of the fox (V. vulpes), using ~1,000 radiographs of foxes from populations used in the genetic analysis of behavior and morphology. Careful measurements from this robust data base demonstrate that: 1) DA occurs in the limb bones, the ileum, and ischium and in the mandible; 2) regardless of the direction of the length asymmetry vector of a particular skeletal unit, the vectorial direction of length is always opposite to that of width; 3) with the exception of the humerus and radius, there is no correlation or inverse correlation between vectorial amplitudes or magnitudes of bone asymmetries. 4) Postnatal measurements on foxes demonstrate that the asymmetry increases after birth and continues to change (increasing or decreasing) during postnatal growth. 5) A behavior test for preferential use of a specific forelimb exhibited fluctuating asymmetry but not DA. None of the skeletal asymmetries were significantly correlated with a preferential use of a specific forelimb. We suggest that for the majority of fox skeletal parameters, growth on the right and left side of the fox are differentially biased resulting in fixed differences between the two sides in either the rate of growth or the length of the period during which growth occurs. Random effects around these fixed differences perturb the magnitude of the effects such that the magnitudes of length and width asymmetries are not inversely correlated at the level of individual animals.
doi:10.1002/jmor.10890
PMCID: PMC3057660  PMID: 20862692
fox; V. vulpes; skeleton; directional asymmetry; pelvis; mandible; limb bone
4.  Comparison of Metal Concentrations in Bones of Long-Living Mammals 
Biological Trace Element Research  2013;152(2):195-203.
The aim of this study was to compare zinc, copper, lead, cadmium, and mercury concentrations in the bones of long-living mammals—humans (Homo sapiens) and Canidae (dogs Canis familiaris and foxes Vulpes vulpes) from northwestern Poland and to determine the usefulness of Canidae as bioindicators of environmental exposure to metals in humans. Zinc concentrations in cartilage with adjacent compact bone and in spongy bone were highest in foxes (∼120 mg/kg dry weight (dw)) and lowest in dogs (80 mg/kg dw). Copper concentrations in cartilage with adjacent compact bone were greatest in foxes (1.17 mg/kg dw) and smallest in humans (∼0.8 mg/kg dw), while in spongy bone they were greatest in dogs (0.76 mg/kg dw) and lowest in foxes (0.45 mg/kg dw). Lead concentrations in both analyzed materials were highest in dogs (>3 mg/kg dw) and lowest in humans (>0.6 mg/kg dw). Cadmium concentration, also in both the analyzed materials, were highest in foxes (>0.15 mg/kg dw) and lowest in humans (>0.04 mg/kg dw). Mercury concentration in bones was low and did not exceed 0.004 mg/kg dw in all the examined species. The concentrations of essential metals in the bones of the examined long-living mammals were similar. The different concentrations of toxic metals were due to environmental factors. As bone tissues are used in the assessment of the long-term effects of environmental exposure to heavy metals on the human body, ecotoxicological studies on the bones of domesticated and wild long-living mammals, including Canidae, may constitute a significant supplement to this research.
doi:10.1007/s12011-013-9615-x
PMCID: PMC3624004  PMID: 23377610
Human; Dog; Red fox; Bioindicator; Bone tissue; Trace elements
5.  Molecular evolution of the leptin exon 3 in some species of the family Canidae 
The structure of the leptin gene seems to be well conserved. The polymorphism of this gene in four species belonging to the Canidae family (the dog (Canis familiaris) – 16 different breeds, the Chinese racoon dog (Nyctereutes procyonoides procyonoides), the red fox (Vulpes vulpes) and the arctic fox (Alopex lagopus)) were studied with the use of single strand conformation polymorphism (SSCP), restriction fragment length polymorphism (RFLP) and DNA sequencing techniques. For exon 2, all species presented the same SSCP pattern, while in exon 3 some differences were found. DNA sequencing of exon 3 revealed the presence of six nucleotide substitutions, differentiating the studied species. Three of them cause amino acid substitutions as well. For all dog breeds studied, SSCP patterns were identical.
doi:10.1186/1297-9686-35-6-573
PMCID: PMC2697982  PMID: 12939206
leptin; Canidae; polymorphism
6.  Kind granddaughters of angry grandmothers: the effect of domestication on vocalization in cross-bred silver foxes 
Behavioural processes  2009;81(3):369.
The genetic basis of the effects of domestication have previously been examined in relation to morphological, physiological and behavioural traits, but not for vocalizations. According to Belyaev (1979, Journal of Heredity 70, 301-308), directional selection for tame behaviour toward humans resulted in domestication. This hypothesis has been confirmed experimentally on the farm-bred silver fox Vulpes vulpes population that has undergone 45 years of artificial selection for tameness and 35 years of selection for aggressiveness. These foxes, with their precisely known attitudes toward people, provide a means of examining vocal indicators of tameness and aggressiveness to establish the genetic basis for vocal production in canids. We examined vocalizations toward people in foxes selected for tameness and aggressiveness compared to those of three kinds of crosses: Hybrids (Tame X Aggressive), A-Backcrosses (Aggressive X Hybrid) and T-Backcrosses (Tame X Hybrid). We report the effects of selection for tameness on usage and structure of different vocalisations and suggest that vocal indicators for tameness and aggressiveness toward people are discrete phenotypic traits in silver foxes.
doi:10.1016/j.beproc.2009.03.012
PMCID: PMC2814310  PMID: 19520236
behaviour genetic; canid-human interaction; Canidae; domestication; vocal behaviour; Vulpes vulpes
7.  Combining information from surveys of several species to estimate the probability of freedom from Echinococcus multilocularis in Sweden, Finland and mainland Norway 
Background
The fox tapeworm Echinococcus multilocularis has foxes and other canids as definitive host and rodents as intermediate hosts. However, most mammals can be accidental intermediate hosts and the larval stage may cause serious disease in humans. The parasite has never been detected in Sweden, Finland and mainland Norway. All three countries require currently an anthelminthic treatment for dogs and cats prior to entry in order to prevent introduction of the parasite. Documentation of freedom from E. multilocularis is necessary for justification of the present import requirements.
Methods
The probability that Sweden, Finland and mainland Norway were free from E. multilocularis and the sensitivity of the surveillance systems were estimated using scenario trees. Surveillance data from five animal species were included in the study: red fox (Vulpes vulpes), raccoon dog (Nyctereutes procyonoides), domestic pig, wild boar (Sus scrofa) and voles and lemmings (Arvicolinae).
Results
The cumulative probability of freedom from EM in December 2009 was high in all three countries, 0.98 (95% CI 0.96-0.99) in Finland and 0.99 (0.97-0.995) in Sweden and 0.98 (0.95-0.99) in Norway.
Conclusions
Results from the model confirm that there is a high probability that in 2009 the countries were free from E. multilocularis. The sensitivity analyses showed that the choice of the design prevalences in different infected populations was influential. Therefore more knowledge on expected prevalences for E. multilocularis in infected populations of different species is desirable to reduce residual uncertainty of the results.
doi:10.1186/1751-0147-53-9
PMCID: PMC3049754  PMID: 21314948
8.  A Simple Genetic Architecture Underlies Morphological Variation in Dogs 
PLoS Biology  2010;8(8):e1000451.
The largest genetic study to date of morphology in domestic dogs identifies genes controlling nearly 100 morphological traits and identifies important trends in phenotypic variation within this species.
Domestic dogs exhibit tremendous phenotypic diversity, including a greater variation in body size than any other terrestrial mammal. Here, we generate a high density map of canine genetic variation by genotyping 915 dogs from 80 domestic dog breeds, 83 wild canids, and 10 outbred African shelter dogs across 60,968 single-nucleotide polymorphisms (SNPs). Coupling this genomic resource with external measurements from breed standards and individuals as well as skeletal measurements from museum specimens, we identify 51 regions of the dog genome associated with phenotypic variation among breeds in 57 traits. The complex traits include average breed body size and external body dimensions and cranial, dental, and long bone shape and size with and without allometric scaling. In contrast to the results from association mapping of quantitative traits in humans and domesticated plants, we find that across dog breeds, a small number of quantitative trait loci (≤3) explain the majority of phenotypic variation for most of the traits we studied. In addition, many genomic regions show signatures of recent selection, with most of the highly differentiated regions being associated with breed-defining traits such as body size, coat characteristics, and ear floppiness. Our results demonstrate the efficacy of mapping multiple traits in the domestic dog using a database of genotyped individuals and highlight the important role human-directed selection has played in altering the genetic architecture of key traits in this important species.
Author Summary
Dogs offer a unique system for the study of genes controlling morphology. DNA from 915 dogs from 80 domestic breeds, as well as a set of feral dogs, was tested at over 60,000 points of variation and the dataset analyzed using novel methods to find loci regulating body size, head shape, leg length, ear position, and a host of other traits. Because each dog breed has undergone strong selection by breeders to have a particular appearance, there is a strong footprint of selection in regions of the genome that are important for controlling traits that define each breed. These analyses identified new regions of the genome, or loci, that are important in controlling body size and shape. Our results, which feature the largest number of domestic dogs studied at such a high level of genetic detail, demonstrate the power of the dog as a model for finding genes that control the body plan of mammals. Further, we show that the remarkable diversity of form in the dog, in contrast to some other species studied to date, appears to have a simple genetic basis dominated by genes of major effect.
doi:10.1371/journal.pbio.1000451
PMCID: PMC2919785  PMID: 20711490
9.  Evolution of adaptive phenotypic variation patterns by direct selection for evolvability 
A basic assumption of the Darwinian theory of evolution is that heritable variation arises randomly. In this context, randomness means that mutations arise irrespective of the current adaptive needs imposed by the environment. It is broadly accepted, however, that phenotypic variation is not uniformly distributed among phenotypic traits, some traits tend to covary, while others vary independently, and again others barely vary at all. Furthermore, it is well established that patterns of trait variation differ among species. Specifically, traits that serve different functions tend to be less correlated, as for instance forelimbs and hind limbs in bats and humans, compared with the limbs of quadrupedal mammals. Recently, a novel class of genetic elements has been identified in mouse gene-mapping studies that modify correlations among quantitative traits. These loci are called relationship loci, or relationship Quantitative Trait Loci (rQTL), and affect trait correlations by changing the expression of the existing genetic variation through gene interaction. Here, we present a population genetic model of how natural selection acts on rQTL. Contrary to the usual neo-Darwinian theory, in this model, new heritable phenotypic variation is produced along the selected dimension in response to directional selection. The results predict that selection on rQTL leads to higher correlations among traits that are simultaneously under directional selection. On the other hand, traits that are not simultaneously under directional selection are predicted to evolve lower correlations. These results and the previously demonstrated existence of rQTL variation, show a mechanism by which natural selection can directly enhance the evolvability of complex organisms along lines of adaptive change.
doi:10.1098/rspb.2010.2113
PMCID: PMC3097830  PMID: 21106581
modularity; allometry; canalization; differential epistasis
10.  Persistence of antibodies in blood and body fluids in decaying fox carcasses, as exemplified by antibodies against Microsporum canis 
To assist in evaluating serological test results from dead animals, 10 silver foxes (Vulpes vulpes) and 10 blue foxes (Alopex lagopus), 6 of each species previously vaccinated against and all challenged with Microsporum canis, were blood sampled and euthanased. Fox carcasses were stored at +10°C, and autopsy was performed on Days 0, 2, 4, 7, and 11 post mortem during which samples from blood and/or body fluid from the thoracic cavity were collected. Antibodies against M. canis were measured in an enzyme-linked immunosorbent assay (ELISA) as absorbance values (optical density; OD). To assess the degradation of antibodies, the ratio between post mortem and ante mortem absorbance was calculated. The mean absorbance from samples collected during autopsy was generally lower than from samples from live animals. In blood samples, this difference increased significantly with time (P = 0.04), while in body fluid samples the difference decreased (not significant; P = 0.18). We suggest that a positive serological result from testing blood or body fluid of a dead animal may be regarded as valuable, although specific prevalences obtained by screening populations based on this type of material may represent an under-estimation of the true antibody prevalence. Negative serological test results based on material from carcasses may be less conclusive, taken into account the general degradation processes in decaying carcasses, also involving immunoglobulin proteins.
doi:10.1186/1751-0147-48-10
PMCID: PMC1553463  PMID: 16987389
11.  On the origin of a domesticated species: Identifying the parent population of Russian silver foxes (Vulpes vulpes) 
The foxes at Novosibirsk, Russia, are the only population of domesticated foxes in the world. These domesticated foxes originated from farm-bred silver foxes (Vulpes vulpes), whose genetic source is unknown. In this study we examined the origin of the domesticated strain of foxes and two other farm-bred fox populations (aggressive and unselected) maintained in Novosibirsk. To identify the phylogenetic origin of these populations we sequenced two regions of mtDNA, cytochrome b and D-loop, from 24 Novosibirsk foxes (8 foxes from each population) and compared them with corresponding sequences of native red foxes from Europe, Asia, Alaska and Western Canada, Eastern Canada, and the Western Mountains of the USA. We identified seven cytochrome b - D-loop haplotypes in Novosibirsk populations, four of which were previously observed in Eastern North America. The three remaining haplotypes differed by one or two base change from the most common haplotype in Eastern Canada. ΦST analysis showed significant differentiation between Novosibirsk populations and red fox populations from all geographic regions except Eastern Canada. No haplotypes of Eurasian origin were identified in the Novosibirsk populations. These results are consistent with historical records indicating that the original breeding stock of farm-bred foxes originated from Prince Edward Island, Canada. Mitochondrial DNA data together with historical records indicate two stages in the selection of domesticated foxes: the first includes captive breeding for ~50 years with unconscious selection for behaviour; the second corresponds to over 50 further years of intensive selection for tame behaviour.
doi:10.1111/j.1095-8312.2011.01629.x
PMCID: PMC3101803  PMID: 21625363
domestication; mitochondrial DNA; phylogeography; red fox; tameness
12.  Frequency distribution of Echinococcus multilocularis and other helminths of foxes in Kyrgyzstan 
Veterinary parasitology  2010;171(3-4):286-292.
Echinococcosis is a major emerging zoonosis in central Asia. A study of the helminth fauna of foxes from Naryn Oblast in central Kyrgyzstan was undertaken to investigate the abundance of Echinococcus multilocularis in a district where a high prevalence of this parasite had previously been detected in dogs. A total of 151 foxes (Vulpes vulpes) were investigated in a necropsy study. Of these 96 (64%) were infected with E. multilocularis with a mean abundance of 8669 parasites per fox. This indicates that red foxes are a major definitive host of E. multilocularis in this country. This also demonstrates that the abundance and prevalence of E. multilocularis in the natural definitive host are likely to be high in geographical regions where there is a concomitant high prevalence in alternative definitive hosts such as dogs. In addition Mesocestoides spp., Dipylidium caninum, Taenia spp., Toxocara canis, Toxascaris leonina, Capillaria and Acanthocephala spp. were found in 99 (66%), 50 (33%), 48 (32%), 46 (30%), 9 (6%), 34 (23%) and 2 (1%) of foxes, respectively. The prevalence but not the abundance of E. multilocularis decreased with age. The abundance of Dipylidium caninum also decreased with age. The frequency distribution of E. multilocularis and Mesocestoides spp. followed a zero inflated negative binomial distribution, whilst all other helminths had a negative binomial distribution. This demonstrates that the frequency distribution of positive counts and not just the frequency of zeros in the data set can determine if a zero inflated or non-zero inflated model is more appropriate. This is because the prevalences of E. multolocularis and Mesocestoides spp. were the highest (and hence had fewest zero counts) yet the parasite distribution nevertheless gave a better fit to the zero inflated models.
doi:10.1016/j.vetpar.2010.04.006
PMCID: PMC2903646  PMID: 20434845
Fox; intestinal helminths; Echinococcus multilocularis; Kyrgyzstan; epidemiology; zero inflated; negative binomial
13.  Sequence comparison of prefrontal cortical brain transcriptome from a tame and an aggressive silver fox (Vulpes vulpes) 
BMC Genomics  2011;12:482.
Background
Two strains of the silver fox (Vulpes vulpes), with markedly different behavioral phenotypes, have been developed by long-term selection for behavior. Foxes from the tame strain exhibit friendly behavior towards humans, paralleling the sociability of canine puppies, whereas foxes from the aggressive strain are defensive and exhibit aggression to humans. To understand the genetic differences underlying these behavioral phenotypes fox-specific genomic resources are needed.
Results
cDNA from mRNA from pre-frontal cortex of a tame and an aggressive fox was sequenced using the Roche 454 FLX Titanium platform (> 2.5 million reads & 0.9 Gbase of tame fox sequence; >3.3 million reads & 1.2 Gbase of aggressive fox sequence). Over 80% of the fox reads were assembled into contigs. Mapping fox reads against the fox transcriptome assembly and the dog genome identified over 30,000 high confidence fox-specific SNPs. Fox transcripts for approximately 14,000 genes were identified using SwissProt and the dog RefSeq databases. An at least 2-fold expression difference between the two samples (p < 0.05) was observed for 335 genes, fewer than 3% of the total number of genes identified in the fox transcriptome.
Conclusions
Transcriptome sequencing significantly expanded genomic resources available for the fox, a species without a sequenced genome. In a very cost efficient manner this yielded a large number of fox-specific SNP markers for genetic studies and provided significant insights into the gene expression profile of the fox pre-frontal cortex; expression differences between the two fox samples; and a catalogue of potentially important gene-specific sequence variants. This result demonstrates the utility of this approach for developing genomic resources in species with limited genomic information.
doi:10.1186/1471-2164-12-482
PMCID: PMC3199282  PMID: 21967120
14.  Transcriptional heterochrony in talpid mole autopods 
EvoDevo  2012;3:16.
Background
Talpid moles show many specializations in their adult skeleton linked to fossoriality, including enlarged hands when compared to the feet. Heterochrony in developmental mechanisms is hypothesized to account for morphological evolution in skeletal elements.
Methods
The temporal and spatial distribution of SOX9 expression, which is an early marker of chondrification, is analyzed in autopods of the fossorial Iberian mole Talpa occidentalis, as well as in shrew (Cryptotis parva) and mouse (Mus musculus) for comparison.
Results and discussion
SOX9 expression is advanced in the forelimb compared to the hind limb in the talpid mole. In contrast, in the shrew and the mouse, which do not show fossorial specializations in their autopods, it is synchronous. We provide evidence that transcriptional heterochrony affects the development of talpid autopods, an example of developmental penetrance. We discuss our data in the light of earlier reported pattern heterochrony and later morphological variation in talpid limbs.
Conclusion
Transcriptional heterochrony in SOX9 expression is found in talpid autopods, which is likely to account for pattern heterochrony in chondral limb development as well as size variation in adult fore- and hind limbs.
doi:10.1186/2041-9139-3-16
PMCID: PMC3441920  PMID: 22873211
SOX9 expression; Developmental penetrance; Talpidae
15.  Exploring reservoir dynamics: a case study of rabies in the Serengeti ecosystem 
The Journal of applied ecology  2008;45(4):1246-1257.
Summary
Knowledge of infection reservoir dynamics is critical for effective disease control, but identifying reservoirs of multi-host pathogens is challenging. Here, we synthesize several lines of evidence to investigate rabies reservoirs in complex carnivore communities of the Serengeti ecological region in northwest Tanzania, where the disease has been confirmed in 12 carnivore species.Long-term monitoring data suggest that rabies persists in high-density domestic dog Canis familiaris populations (> 11 dogs km−2) and occurs less frequently in lower-density (< 5 dogs km−2) populations and only sporadically in wild carnivores.Genetic data show that a single rabies virus variant belonging to the group of southern Africa canid-associated viruses (Africa 1b) circulates among a range of species, with no evidence of species-specific virus–host associations.Within-species transmission was more frequently inferred from high-resolution epidemiological data than between-species transmission. Incidence patterns indicate that spill-over of rabies from domestic dog populations sometimes initiates short-lived chains of transmission in other carnivores.Synthesis and applications. The balance of evidence suggests that the reservoir of rabies in the Serengeti ecosystem is a complex multi-host community where domestic dogs are the only population essential for persistence, although other carnivores contribute to the reservoir as non-maintenance populations. Control programmes that target domestic dog populations should therefore have the greatest impact on reducing the risk of infection in all other species including humans, livestock and endangered wildlife populations, but transmission in other species may increase the level of vaccination coverage in domestic dog populations necessary to eliminate rabies.
doi:10.1111/j.1365-2664.2008.01468.x
PMCID: PMC3303133  PMID: 22427710
carnivore; infectious disease; multi-host; phylogeny; rabies; reservoir; spill-over; transmission
16.  Cholesterol Metabolism: the Main Pathway Acting Downstream of Cytochrome P450 Oxidoreductase in Skeletal Development of the Limb▿ †  
Molecular and Cellular Biology  2009;29(10):2716-2729.
Cytochrome P450 oxidoreductase (POR) is the obligate electron donor for all microsomal cytochrome P450 enzymes, which catalyze the metabolism of a wide spectrum of xenobiotic and endobiotic compounds. Point mutations in POR have been found recently in patients with Antley-Bixler-like syndrome, which includes limb skeletal defects. In order to study P450 function during limb and skeletal development, we deleted POR specifically in mouse limb bud mesenchyme. Forelimbs and hind limbs in conditional knockout (CKO) mice were short with thin skeletal elements and fused joints. POR deletion occurred earlier in forelimbs than in hind limbs, leading additionally to soft tissue syndactyly and loss of wrist elements and phalanges due to changes in growth, cell death, and skeletal segmentation. Transcriptional analysis of E12.5 mouse forelimb buds demonstrated the expression of P450s involved in retinoic acid, cholesterol, and arachidonic acid metabolism. Biochemical analysis of CKO limbs confirmed retinoic acid excess. In CKO limbs, expression of genes throughout the whole cholesterol biosynthetic pathway was upregulated, and cholesterol deficiency can explain most aspects of the phenotype. Thus, cellular POR-dependent cholesterol synthesis is essential during limb and skeletal development. Modulation of P450 activity could contribute to susceptibility of the embryo and developing organs to teratogenesis.
doi:10.1128/MCB.01638-08
PMCID: PMC2682028  PMID: 19273610
17.  Parallel Mapping and Simultaneous Sequencing Reveals Deletions in BCAN and FAM83H Associated with Discrete Inherited Disorders in a Domestic Dog Breed 
PLoS Genetics  2012;8(1):e1002462.
The domestic dog (Canis familiaris) segregates more naturally-occurring diseases and phenotypic variation than any other species and has become established as an unparalled model with which to study the genetics of inherited traits. We used a genome-wide association study (GWAS) and targeted resequencing of DNA from just five dogs to simultaneously map and identify mutations for two distinct inherited disorders that both affect a single breed, the Cavalier King Charles Spaniel. We investigated episodic falling (EF), a paroxysmal exertion-induced dyskinesia, alongside the phenotypically distinct condition congenital keratoconjunctivitis sicca and ichthyosiform dermatosis (CKCSID), commonly known as dry eye curly coat syndrome. EF is characterised by episodes of exercise-induced muscular hypertonicity and abnormal posturing, usually occurring after exercise or periods of excitement. CKCSID is a congenital disorder that manifests as a rough coat present at birth, with keratoconjunctivitis sicca apparent on eyelid opening at 10–14 days, followed by hyperkeratinisation of footpads and distortion of nails that develops over the next few months. We undertook a GWAS with 31 EF cases, 23 CKCSID cases, and a common set of 38 controls and identified statistically associated signals for EF and CKCSID on chromosome 7 (Praw 1.9×10−14; Pgenome = 1.0×10−5) and chromosome 13 (Praw 1.2×10−17; Pgenome = 1.0×10−5), respectively. We resequenced both the EF and CKCSID disease-associated regions in just five dogs and identified a 15,724 bp deletion spanning three exons of BCAN associated with EF and a single base-pair exonic deletion in FAM83H associated with CKCSID. Neither BCAN or FAM83H have been associated with equivalent disease phenotypes in any other species, thus demonstrating the ability to use the domestic dog to study the genetic basis of more than one disease simultaneously in a single breed and to identify multiple novel candidate genes in parallel.
doi:10.1371/journal.pgen.1002462
PMCID: PMC3257292  PMID: 22253609
18.  Selection for tameness modulates the expression of heme related genes in silver foxes 
Background
The genetic and molecular mechanisms of tameness are largely unknown. A line of silver foxes (Vulpes vulpes) selected for non-aggressive behavior has been used in Russia since the 1960's to study the effect of domestication. We have previously compared descendants of these selected (S) animals with a group of non-selected (NS) silver foxes kept under identical conditions, and showed that changes in the brain transcriptome between the two groups are small. Unexpectedly, many of the genes showing evidence of differential expression between groups were related to hemoproteins.
Results
In this study, we use quantitative RT-PCR to demonstrate that the activity of heme related genes differ between S and NS foxes in three regions of the brain. Furthermore, our analyses also indicate that changes in mRNA levels of heme related genes can be well described by an additive polygenic effect. We also show that the difference in genetic background between the two lines of foxes is limited, as estimated by mitochondrial DNA divergence.
Conclusion
Our results indicate that selection for tameness can modify the expression of heme related genes in canid brain regions known to modulate emotions and behavior. The possible involvement of heme related genes in behavior is surprising. It is possible that hemoglobin modulates the behavior of canids by interaction with CO and NO signaling. Another possibility is that hemorphins, known to be produced after enzymatic cleavage of hemoglobin, are responsible for behavioral alterations. Thus, we hypothesize that hemoglobin metabolism can be a functionally relevant aspect of the domestic phenotype in foxes selected for tameness.
doi:10.1186/1744-9081-3-18
PMCID: PMC1858698  PMID: 17439650
19.  Effects of selection for behavior, human approach mode and sex on vocalization in silver fox 
Journal of ethology  2012;31(1):95-100.
This study presents a first direct comparison of vocal type, call rate and time spent vocalizing among Unselected, Tame and Aggressive strains of silver fox (Vulpes vulpes) in three modes of human approach (Provoking, Approach–Retreat, and Static). Also, it provides a first comparison of male and female vocal output in the Provoking test. Vocal types were found strain-specific irrespective of the fox sex or the test. Males had higher call rates and spent shorter times vocalizing than females. These results support the evidence of genetic-based emotional states, triggering vocal behavior in silver fox strains, and suggest sex dimorphism in vocal activity toward humans.
doi:10.1007/s10164-012-0353-x
PMCID: PMC3601802  PMID: 23525128
Call; Domestication; Human approach test; Gender effect; Canidae
20.  Rhesus monkeys correctly read the goal-relevant gestures of a human agent 
When humans point, they reveal to others their underlying intent to communicate about some distant goal. A controversy has recently emerged based on a broad set of comparative and phylogenetically relevant data. In particular, whereas chimpanzees (Pan troglodytes) have difficulty in using human-generated communicative gestures and actions such as pointing and placing symbolic markers to find hidden rewards, domesticated dogs (Canis familiaris) and silver foxes (Urocyon cinereoargenteus) readily use such gestures and markers. These comparative data have led to the hypothesis that the capacity to infer communicative intent in dogs and foxes has evolved as a result of human domestication. Though this hypothesis has met with challenges, due in part to studies of non-domesticated, non-primate animals, there remains the fundamental question of why our closest living relatives, the chimpanzees, together with other non-human primates, generally fail to make inferences about a target goal of an agent's communicative intent. Here, we add an important wrinkle to this phylogenetic pattern by showing that free-ranging rhesus monkeys (Macaca mulatta) draw correct inferences about the goals of a human agent, using a suite of communicative gestures to locate previously concealed food. Though domestication and human enculturation may play a significant role in tuning up the capacity to infer intentions from communicative gestures, these factors are not necessary.
doi:10.1098/rspb.2007.0586
PMCID: PMC2270939  PMID: 17540661
communicative intent; goals; gestures; phylogeny; primates
21.  Pearsonema (syn Capillaria) plica associated cystitis in a Fennoscandian arctic fox (Vulpes lagopus: a case report 
The bladderworm Pearsonema (syn Capillaria) plica affects domestic dogs and wild carnivores worldwide. A high prevalence in red foxes (Vulpes vulpes) has been reported in many European countries. P. plica inhabits the lower urinary tract and is considered to be of low pathogenic significance in dogs mostly causing asymptomatic infections. However, a higher level of pathogenicity has been reported in foxes. A severe cystitis associated with numerous bladderworms was found in a captive arctic fox (Vulpes lagopus) originating from the endangered Fennoscandian arctic fox population. To our knowledge this is the first description of P. plica infection in an arctic fox.
doi:10.1186/1751-0147-52-39
PMCID: PMC2892499  PMID: 20540788
22.  Genetic Recombination Is Targeted towards Gene Promoter Regions in Dogs 
PLoS Genetics  2013;9(12):e1003984.
The identification of the H3K4 trimethylase, PRDM9, as the gene responsible for recombination hotspot localization has provided considerable insight into the mechanisms by which recombination is initiated in mammals. However, uniquely amongst mammals, canids appear to lack a functional version of PRDM9 and may therefore provide a model for understanding recombination that occurs in the absence of PRDM9, and thus how PRDM9 functions to shape the recombination landscape. We have constructed a fine-scale genetic map from patterns of linkage disequilibrium assessed using high-throughput sequence data from 51 free-ranging dogs, Canis lupus familiaris. While broad-scale properties of recombination appear similar to other mammalian species, our fine-scale estimates indicate that canine highly elevated recombination rates are observed in the vicinity of CpG rich regions including gene promoter regions, but show little association with H3K4 trimethylation marks identified in spermatocytes. By comparison to genomic data from the Andean fox, Lycalopex culpaeus, we show that biased gene conversion is a plausible mechanism by which the high CpG content of the dog genome could have occurred.
Author Summary
Recombination in mammalian genomes tends to occur within highly localized regions known as recombination hotspots. These hotspots appear to be a ubiquitous feature of mammalian genomes, but tend to not be shared between closely related species despite high levels of DNA sequence similarity. This disparity has been largely explained by the discovery of PRDM9 as the gene responsible for localizing recombination hotspots via recognition and binding to specific DNA motifs. Variation within PRDM9 can lead to changes to the recognized motif, and hence changes to the location of recombination hotspots thought the genome. Multiple studies have shown that PRDM9 is under strong selective pressure, apparently leading to a rapid turnover of hotspot locations between species. However, uniquely amongst mammals, PRDM9 appears to be dysfunctional in dogs and other canids. In this paper, we investigate how the loss of PRDM9 has affected the fine-scale recombination landscape in dogs and contrast this with patterns seen in other species.
doi:10.1371/journal.pgen.1003984
PMCID: PMC3861134  PMID: 24348265
23.  GREMLIN1 IS REQUIRED FOR SKELETAL DEVELOPMENT AND POSTNATAL SKELETAL HOMEOSTASIS 
Journal of cellular physiology  2012;227(1):269-277.
Gremlin is an antagonist of bone morphogenetic proteins, and its overexpression causes suppressed osteoblastogenesis and osteopenia. Inactivation of Grem1 results in severe developmental defects, but the consequences of the global inactivation of Grem1 on the postnatal skeleton are not known. To study the function of gremlin, Grem1 was inactivated by homologous recombination, and mice were maintained in a C57BL/6/FVB mixed genetic background due to embryonic and neonatal lethality in the uniform C57BL/6 background. Grem1 null mice exhibited developmental skeletal abnormalities, leading to incomplete formation of metatarsal bones and of fore limbs and hind limbs. Grem1 null mice exhibited decreased weight and body fat and shortened femoral length. Bone histomorphometric and microarchitectural analyses of distal femurs revealed decreased bone volume and increased bone formation in 1 month old Grem1 null mice. Trabecular femoral bone volume was restored in older Grem1 null female mice, and to a lesser extent in male mice. Vertebral microarchitecture confirmed the osteopenia observed in 1 month old Grem1 null mice and demonstrated recovery of trabecular bone in older female, but not in older male Grem1 null mice, which exhibited persistent vertebral osteopenia. In conclusion, Grem1 is not only necessary for skeletal development, but also for postnatal skeletal homeostasis; its inactivation causes osteopenia, which is partially reversed in a spatial, temporal and sex-dependent manner due to an increase in bone formation.
doi:10.1002/jcp.22730
PMCID: PMC3132213  PMID: 21412775
bone formation; bone morphogenetic protein (BMP); BMP antagonists; noggin; gremlin
24.  A Shared System of Representation Governing Quantity Discrimination in Canids 
One way to investigate the evolution of cognition is to compare the abilities of phylogenetically related species. The domestic dog (Canis lupus familiaris), for example, still shares cognitive abilities with the coyote (Canis latrans). Both of these canids possess the ability to make psychophysical “less/more” discriminations of food based on quantity. Like many other species including humans, this ability is mediated by Weber’s Law: discrimination of continuous quantities is dependent on the ratio between the two quantities. As two simultaneously presented quantities of food become more similar, choice of the large or small option becomes random in both dogs and coyotes. It remains unknown, however, whether these closely related species within the same family – one domesticated, and one wild – make such quantitative comparisons with comparable accuracy. Has domestication honed or diminished this quantitative ability? Might different selective and ecological pressures facing coyotes drive them to be more or less able to accurately represent and discriminate food quantity than domesticated dogs? This study is an effort to elucidate this question concerning the evolution of non-verbal quantitative cognition. Here, we tested the quantitative discrimination ability of 16 domesticated dogs. Each animal was given nine trials in which two different quantities of food were simultaneously displayed to them. The domesticated dogs’ performance on this task was then compared directly to the data from 16 coyotes’ performance on this same task reported by Baker et al. (2011). The quantitative discrimination abilities between the two species were strikingly similar. Domesticated dogs demonstrated similar quantitative sensitivity as coyotes, suggesting that domestication may not have significantly altered the psychophysical discrimination abilities of canids. Instead, this study provides further evidence for similar non-verbal quantitative abilities across multiple species.
doi:10.3389/fpsyg.2012.00387
PMCID: PMC3465982  PMID: 23060847
Weber’s law; canid; quantity discrimination
25.  Quantitative Phenotyping of Duchenne Muscular Dystrophy Dogs by Comprehensive Gait Analysis and Overnight Activity Monitoring 
PLoS ONE  2013;8(3):e59875.
The dystrophin-deficient dog is excellent large animal model for testing novel therapeutic modalities for Duchenne muscular dystrophy (DMD). Despite well-documented descriptions of dystrophic symptoms in these dogs, very few quantitative studies have been performed. Here, we developed a comprehensive set of non-invasive assays to quantify dog gait (stride length and speed), joint angle and limb mobility (for both forelimb and hind limb), and spontaneous activity at night. To validate these assays, we examined three 8-m-old mix-breed dystrophic dogs. We also included three age-matched siblings as the normal control. High-resolution video recorders were used to digitize dog walking and spontaneous movement at night. Stride speed and length were significantly decreased in affected dogs. The mobility of the limb segments (forearm, front foot, lower thigh, rear foot) and the carpus and hock joints was significantly reduced in dystrophic dogs. There was also a significant reduction of the movement in affected dogs during overnight monitoring. In summary, we have established a comprehensive set of outcome measures for clinical phenotyping of DMD dogs. These non-invasive end points would be valuable in monitoring disease progression and therapeutic efficacy in translational studies in the DMD dog model.
doi:10.1371/journal.pone.0059875
PMCID: PMC3609742  PMID: 23544107

Results 1-25 (262399)