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1.
Annu Rev Cell Dev Biol ; 30: 535-60, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25062362

RESUMEN

Although most modern dog breeds are less than 200 years old, the symbiosis between man and dog is ancient. Since prehistoric times, repeated selection events have transformed the wolf into man's guardians, laborers, athletes, and companions. The rapid transformation from pack predator to loyal companion is a feat that is arguably unique among domesticated animals. How this transformation came to pass remained a biological mystery until recently: Within the past decade, the deployment of genomic approaches to study population structure, detect signatures of selection, and identify genetic variants that underlie canine phenotypes is ushering into focus novel biological mechanisms that make dogs remarkable. Ironically, the very practices responsible for breed formation also spurned morbidity; today, many diseases are correlated with breed identity. In this review, we discuss man's best friend in the context of a genetic model to understand paradigms of heritable phenotypes, both desirable and disadvantageous.


Asunto(s)
Perros/genética , Genoma , Animales , Tamaño Corporal/genética , Neoplasias Óseas/genética , Neoplasias Óseas/veterinaria , Cruzamiento , Mapeo Cromosómico , Modelos Animales de Enfermedad , Enfermedades de los Perros/genética , Perros/anatomía & histología , Perros/clasificación , Extremidades/anatomía & histología , Estudio de Asociación del Genoma Completo , Glicoproteínas/genética , Glicoproteínas/fisiología , Proteína HMGA2/genética , Proteína HMGA2/fisiología , Cabello/anatomía & histología , Cardiopatías/genética , Cardiopatías/veterinaria , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/fisiología , Síndromes Neoplásicos Hereditarios/genética , Síndromes Neoplásicos Hereditarios/veterinaria , Osteosarcoma/genética , Osteosarcoma/veterinaria , Fenotipo , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Selección Genética , Piel/anatomía & histología , Cráneo/anatomía & histología , Proteína Smad2/genética , Proteína Smad2/fisiología , Especificidad de la Especie , Cola (estructura animal)/anatomía & histología
2.
Proc Natl Acad Sci U S A ; 118(11)2021 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-33836575

RESUMEN

Technological advances have allowed improvements in genome reference sequence assemblies. Here, we combined long- and short-read sequence resources to assemble the genome of a female Great Dane dog. This assembly has improved continuity compared to the existing Boxer-derived (CanFam3.1) reference genome. Annotation of the Great Dane assembly identified 22,182 protein-coding gene models and 7,049 long noncoding RNAs, including 49 protein-coding genes not present in the CanFam3.1 reference. The Great Dane assembly spans the majority of sequence gaps in the CanFam3.1 reference and illustrates that 2,151 gaps overlap the transcription start site of a predicted protein-coding gene. Moreover, a subset of the resolved gaps, which have an 80.95% median GC content, localize to transcription start sites and recombination hotspots more often than expected by chance, suggesting the stable canine recombinational landscape has shaped genome architecture. Alignment of the Great Dane and CanFam3.1 assemblies identified 16,834 deletions and 15,621 insertions, as well as 2,665 deletions and 3,493 insertions located on secondary contigs. These structural variants are dominated by retrotransposon insertion/deletion polymorphisms and include 16,221 dimorphic canine short interspersed elements (SINECs) and 1,121 dimorphic long interspersed element-1 sequences (LINE-1_Cfs). Analysis of sequences flanking the 3' end of LINE-1_Cfs (i.e., LINE-1_Cf 3'-transductions) suggests multiple retrotransposition-competent LINE-1_Cfs segregate among dog populations. Consistent with this conclusion, we demonstrate that a canine LINE-1_Cf element with intact open reading frames can retrotranspose its own RNA and that of a SINEC_Cf consensus sequence in cultured human cells, implicating ongoing retrotransposon activity as a driver of canine genetic variation.


Asunto(s)
Perros/genética , Secuencia Rica en GC , Genoma , Secuencias Repetitivas Esparcidas , Animales , Perros/clasificación , Elementos de Nucleótido Esparcido Largo , Elementos de Nucleótido Esparcido Corto , Especificidad de la Especie
3.
PLoS Genet ; 17(5): e1009543, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33983928

RESUMEN

Histiocytic sarcoma is an aggressive hematopoietic malignancy of mature tissue histiocytes with a poorly understood etiology in humans. A histologically and clinically similar counterpart affects flat-coated retrievers (FCRs) at unusually high frequency, with 20% developing the lethal disease. The similar clinical presentation combined with the closed population structure of dogs, leading to high genetic homogeneity, makes dogs an excellent model for genetic studies of cancer susceptibility. To determine the genetic risk factors underlying histiocytic sarcoma in FCRs, we conducted multiple genome-wide association studies (GWASs), identifying two loci that confer significant risk on canine chromosomes (CFA) 5 (Pwald = 4.83x10-9) and 19 (Pwald = 2.25x10-7). We subsequently undertook a multi-omics approach that has been largely unexplored in the canine model to interrogate these regions, generating whole genome, transcriptome, and chromatin immunoprecipitation sequencing. These data highlight the PI3K pathway gene PIK3R6 on CFA5, and proximal candidate regulatory variants that are strongly associated with histiocytic sarcoma and predicted to impact transcription factor binding. The CFA5 association colocalizes with susceptibility loci for two hematopoietic malignancies, hemangiosarcoma and B-cell lymphoma, in the closely related golden retriever breed, revealing the risk contribution this single locus makes to multiple hematological cancers. By comparison, the CFA19 locus is unique to the FCR and harbors risk alleles associated with upregulation of TNFAIP6, which itself affects cell migration and metastasis. Together, these loci explain ~35% of disease risk, an exceptionally high value that demonstrates the advantages of domestic dogs for complex trait mapping and genetic studies of cancer susceptibility.


Asunto(s)
Enfermedades de los Perros/genética , Perros/clasificación , Perros/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo/veterinaria , Mutación de Línea Germinal/genética , Neoplasias Hematológicas/veterinaria , Alelos , Animales , Sitios de Unión , Moléculas de Adhesión Celular/genética , Secuenciación de Inmunoprecipitación de Cromatina , Genoma/genética , Genómica , Genotipo , Neoplasias Hematológicas/genética , Sarcoma Histiocítico/genética , Sarcoma Histiocítico/veterinaria , Fosfatidilinositol 3-Quinasa/genética , Análisis de Componente Principal , RNA-Seq , Factores de Transcripción/metabolismo
4.
Nat Rev Genet ; 18(12): 705-720, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28944780

RESUMEN

The domestic dog represents one of the most dramatic long-term evolutionary experiments undertaken by humans. From a large wolf-like progenitor, unparalleled diversity in phenotype and behaviour has developed in dogs, providing a model for understanding the developmental and genomic mechanisms of diversification. We discuss pattern and process in domestication, beginning with general findings about early domestication and problems in documenting selection at the genomic level. Furthermore, we summarize genotype-phenotype studies based first on single nucleotide polymorphism (SNP) genotyping and then with whole-genome data and show how an understanding of evolution informs topics as different as human history, adaptive and deleterious variation, morphological development, ageing, cancer and behaviour.


Asunto(s)
Perros/genética , Polimorfismo de Nucleótido Simple , Secuenciación Completa del Genoma , Animales , Conducta Animal , Enfermedades de los Perros/genética , Perros/anatomía & histología , Perros/clasificación , Perros/fisiología , Domesticación , Neoplasias/genética , Neoplasias/veterinaria , Selección Genética , Selección Artificial
5.
Proc Natl Acad Sci U S A ; 117(39): 24369-24376, 2020 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-32868416

RESUMEN

New Guinea singing dogs (NGSD) are identifiable by their namesake vocalizations, which are unlike any other canid population. Their novel behaviors and potential singular origin during dog domestication make them an attractive, but elusive, subject for evolutionary and conservation study. Although once plentiful on the island of New Guinea (NG), they were presumed to currently exist only in captivity. This conclusion was based on the lack of sightings in the lowlands of the island and the concurrent expansion of European- and Asian-derived dogs. We have analyzed the first nuclear genomes from a canid population discovered during a recent expedition to the highlands of NG. The extreme altitude (>4,000 m) of the highland wild dogs' (HWD) observed range and confirmed vocalizations indicate their potential to be a wild NGSD population. Comparison of single-nucleotide polymorphism genotypes shows strong similarity between HWD and the homogeneous captive NGSD, with the HWD showing significantly higher genetic diversity. Admixture analyses and estimation of shared haplotypes with phylogenetically diverse populations also indicates the HWD is a novel population within the distinct evolutionary lineage of Oceanic canids. Taken together, these data indicate the HWD possesses a distinct potential to aid in the conservation of NGSD both in the wild and under human care.


Asunto(s)
Animales Salvajes/genética , Perros/clasificación , Animales , Animales Salvajes/clasificación , Animales Salvajes/fisiología , Perros/genética , Perros/fisiología , Evolución Molecular , Genoma , Nueva Guinea , Filogenia , Polimorfismo de Nucleótido Simple , Canto
6.
PLoS Genet ; 14(12): e1007850, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30521570

RESUMEN

Domestic dog breeds exhibit remarkable morphological variations that result from centuries of artificial selection and breeding. Identifying the genetic changes that contribute to these variations could provide critical insights into the molecular basis of tissue and organismal morphogenesis. Bulldogs, French Bulldogs and Boston Terriers share many morphological and disease-predisposition traits, including brachycephalic skull morphology, widely set eyes and short stature. Unlike other brachycephalic dogs, these breeds also exhibit vertebral malformations that result in a truncated, kinked tail (screw tail). Whole genome sequencing of 100 dogs from 21 breeds identified 12.4 million bi-allelic variants that met inclusion criteria. Whole Genome Association of these variants with the breed defining phenotype of screw tail was performed using 10 cases and 84 controls and identified a frameshift mutation in the WNT pathway gene DISHEVELLED 2 (DVL2) (Chr5: 32195043_32195044del, p = 4.37 X 10-37) as the most strongly associated variant in the canine genome. This DVL2 variant was fixed in Bulldogs and French Bulldogs and had a high allele frequency (0.94) in Boston Terriers. The DVL2 variant segregated with thoracic and caudal vertebral column malformations in a recessive manner with incomplete and variable penetrance for thoracic vertebral malformations between different breeds. Importantly, analogous frameshift mutations in the human DVL1 and DVL3 genes cause Robinow syndrome, a congenital disorder characterized by similar craniofacial, limb and vertebral malformations. Analysis of the canine DVL2 variant protein showed that its ability to undergo WNT-induced phosphorylation is reduced, suggesting that altered WNT signaling may contribute to the Robinow-like syndrome in the screwtail breeds.


Asunto(s)
Anomalías Craneofaciales/veterinaria , Proteínas Dishevelled/genética , Enfermedades de los Perros/genética , Perros/genética , Enanismo/veterinaria , Deformidades Congénitas de las Extremidades/veterinaria , Anomalías Urogenitales/veterinaria , Secuencia de Aminoácidos , Animales , Anomalías Craneofaciales/genética , Anomalías Craneofaciales/metabolismo , Proteínas Dishevelled/metabolismo , Enfermedades de los Perros/metabolismo , Perros/anatomía & histología , Perros/clasificación , Enanismo/genética , Enanismo/metabolismo , Femenino , Mutación del Sistema de Lectura , Variación Genética , Estudio de Asociación del Genoma Completo , Humanos , Deformidades Congénitas de las Extremidades/genética , Deformidades Congénitas de las Extremidades/metabolismo , Masculino , Compuestos de Organosilicio , Homología de Secuencia de Aminoácido , Especificidad de la Especie , Cola (estructura animal)/anatomía & histología , Anomalías Urogenitales/genética , Anomalías Urogenitales/metabolismo , Vía de Señalización Wnt/genética
7.
J Evol Biol ; 33(3): 318-328, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31705702

RESUMEN

Among-population variance of phenotypic traits is of high relevance for understanding evolutionary mechanisms that operate in relatively short timescales, but various sources of nonindependence, such as common ancestry and gene flow, can hamper the interpretations. In this comparative analysis of 138 dog breeds, we demonstrate how such confounders can independently shape the evolution of a behavioural trait (human-directed play behaviour from the Dog Mentality Assessment project). We combined information on genetic relatedness and haplotype sharing to reflect common ancestry and gene flow, respectively, and entered these into a phylogenetic mixed model to partition the among-breed variance of human-directed play behaviour while also accounting for within-breed variance. We found that 75% of the among-breed variance was explained by overall genetic relatedness among breeds, whereas 15% could be attributed to haplotype sharing that arises from gene flow. Therefore, most of the differences in human-directed play behaviour among breeds have likely been caused by constraints of common ancestry as a likely consequence of past selection regimes. On the other hand, gene flow caused by crosses among breeds has played a minor, but not negligible role. Our study serves as an example of an analytical approach that can be applied to comparative situations where the effects of shared origin and gene flow require quantification and appropriate statistical control in a within-species/among-population framework. Altogether, our results suggest that the evolutionary history of dog breeds has left remarkable signatures on the among-breed variation of a behavioural phenotype.


Asunto(s)
Conducta Animal/fisiología , Evolución Biológica , Perros/genética , Flujo Génico , Interacción Humano-Animal , Animales , Cruzamiento , Perros/clasificación , Variación Genética , Haplotipos , Humanos , Filogenia , Juego e Implementos de Juego
8.
PLoS Genet ; 13(3): e1006661, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28257443

RESUMEN

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.


Asunto(s)
Tamaño Corporal/genética , Peso Corporal/genética , Perros/genética , Cromosoma X/genética , Animales , Mapeo Cromosómico/métodos , Perros/clasificación , Femenino , Frecuencia de los Genes , Estudio de Asociación del Genoma Completo/métodos , Genotipo , Proteínas Sustrato del Receptor de Insulina/genética , Masculino , Fenotipo , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADN/métodos , Especificidad de la Especie , Succinato-CoA Ligasas/genética
9.
J Vet Pharmacol Ther ; 43(4): 325-330, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32281146

RESUMEN

The present study aimed to determine the pharmacokinetic profiles of ceftiofur (as measured by ceftiofur and its active metabolites concentrations) in a small-size dog breed, Peekapoo, following a single intravenous or subcutaneous injection of ceftiofur sodium. The study population comprised of five clinically healthy Peekapoo dogs with an average body weight (BW) of 3.4 kg. Each dog received either intravenous or subcutaneous injection, both at 5 mg/kg BW (calculated as pure ceftiofur). Plasma samples were collected at different time points after the administration. Ceftiofur and its active metabolites were extracted from plasma samples, derivatized, and further quantified by high-performance liquid chromatography. The concentrations versus time data were subjected to noncompartmental analysis to obtain the pharmacokinetic parameters. The terminal half-life (t1/2 λz ) was calculated as 7.40 ± 0.79 and 7.91 ± 1.53 hr following intravenous and subcutaneous injections, respectively. After intravenous treatment, the total body clearance (Cl) and volume of distribution at steady-state (VSS ) were determined as 39.91 ± 4.04 ml hr-1  kg-1 and 345.71 ± 28.66 ml/kg, respectively. After subcutaneous injection, the peak concentration (Cmax ; 10.50 ± 0.22 µg/ml) was observed at 3.2 ± 1.1 hr, and the absorption half-life (t1/2 ka ) and absolute bioavailability (F) were calculated as 0.74 ± 0.23 hr and 91.70%±7.34%, respectively. The pharmacokinetic profiles of ceftiofur and its related metabolites demonstrated their quick and excellent absorption after subcutaneous administration, in addition to poor distribution and slow elimination in Peekapoo dogs. Based on the time of concentration above minimum inhibitory concentration (T > MIC) values calculated here, an intravenous or subcutaneous dose at 5 mg/kg of ceftiofur sodium once every 12 hr is predicted to be effective for treating canine bacteria with a MIC value of ≤4.0 µg/ml.


Asunto(s)
Antibacterianos/farmacocinética , Cefalosporinas/farmacocinética , Perros/metabolismo , Animales , Antibacterianos/administración & dosificación , Antibacterianos/sangre , Área Bajo la Curva , Tamaño Corporal , Cefalosporinas/administración & dosificación , Cefalosporinas/sangre , Estudios Cruzados , Perros/clasificación , Femenino , Semivida , Inyecciones Intravenosas/veterinaria , Inyecciones Subcutáneas/veterinaria , Masculino , Distribución Aleatoria
10.
Mamm Genome ; 30(9-10): 289-300, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31414176

RESUMEN

Naturally occurring diseases in dogs provide an important animal model for studying human disease including cancer, heart disease, and autoimmune disorders. Transposable elements (TEs) make up ~ 31% of the dog (Canis lupus familiaris) genome and are one of main drivers to cause genomic variations and alter gene expression patterns of the host genes, which could result in genetic diseases. To detect structural variations (SVs), we conducted whole-genome sequencing of three different breeds, including Maltese, Poodle, and Yorkshire Terrier. Genomic SVs were detected and visualized using BreakDancer program. We identified a total of 2328 deletion SV events in the three breeds compared with the dog reference genome of Boxer. The majority of the genetic variants were found to be TE insertion polymorphism (1229) and the others were TE-mediated deletion (489), non-TE-mediated deletion (542), simple repeat-mediated deletion (32), and other indel (36). Among the TE insertion polymorphism, 286 elements were full-length LINE-1s (L1s). In addition, the 49 SV candidates located in the genic regions were experimentally verified and their polymorphic rates within each breed were examined using PCR assay. Polymorphism analysis of the genomic variants revealed that some of the variants exist polymorphic in the three dog breeds, suggesting that their SV events recently occurred in the dog genome. The findings suggest that TEs have contributed to the genomic variations among the three dog breeds of Maltese, Poodle, and Yorkshire Terrier. In addition, the polymorphic events between the dog breeds indicate that TEs were recently retrotransposed in the dog genome.


Asunto(s)
Perros/genética , Genoma , Animales , Cruzamiento , Elementos Transponibles de ADN , Perros/clasificación , Perros/fisiología , Variación Genética , Mutación INDEL
11.
Proteomics ; 18(3-4)2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29327448

RESUMEN

Saliva is a complex multifunctional fluid that bathes the oral cavity to assist in soft and hard tissue maintenance, lubrication, buffering, defense against microbes, and initiating digestion of foods. It has been extensively characterized in humans but its protein composition in dogs remains poorly characterized, yet saliva composition could explain (patho) physiological differences between individuals, breeds and with humans. This pilot discovery study aimed to characterize canine saliva from two breeds, Labrador retrievers and Beagles, and to compare this with human saliva using quantitative mass spectrometry. The analysis demonstrated considerable inter-individual variation and difference between breeds; however these were small in comparison to the differences between species. Functional mapping suggested roles of detected proteins similar to those found in human saliva with the exception of the initiation of digestion as salivary amylase was lacking or at very low abundance in canine saliva samples. Many potential anti-microbial proteins were detected agreeing with the notion that the oral cavity is under continuous microbial challenge.


Asunto(s)
Perros/clasificación , Perros/metabolismo , Proteoma/análisis , Saliva/química , Proteínas y Péptidos Salivales/metabolismo , Adulto , Animales , Biomarcadores/metabolismo , Cruzamiento , Perros/genética , Femenino , Humanos , Masculino , Espectrometría de Masas , Especificidad de la Especie , Adulto Joven
12.
BMC Genomics ; 19(1): 350, 2018 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-29747566

RESUMEN

BACKGROUND: Most genetic analyses of ancient and modern dogs have focused on variation in the autosomes or on the mitochondria. Mitochondrial DNA is more easily obtained from ancient samples than nuclear DNA and mitochondrial analyses have revealed important insights into the evolutionary history of canids. Utilizing a recently published dog Y-chromosome reference, we analyzed Y-chromosome sequence across a diverse collection of canids and determined the Y haplogroup of three ancient European dogs. RESULTS: We identified 1121 biallelic Y-chromosome SNVs using whole-genome sequences from 118 canids and defined variants diagnostic to distinct dog Y haplogroups. Similar to that of the mitochondria and previous more limited studies of Y diversity, we observe several deep splits in the Y-chromosome tree which may be the result of retained Y-chromosome diversity which predates dog domestication or post-domestication admixture with wolves. We find that Y-chromosomes from three ancient European dogs (4700-7000 years old) belong to distinct clades. CONCLUSIONS: We estimate that the time to the most recent comment ancestor of dog Y haplogroups is 68-151 thousand years ago. Analysis of three Y-chromosomes from the Neolithic confirms long stranding population structure among European dogs.


Asunto(s)
Coyotes/genética , Perros/genética , Evolución Molecular , Haplotipos , Filogenia , Análisis de Secuencia de ADN/métodos , Lobos/genética , Cromosoma Y , Animales , Coyotes/clasificación , ADN Mitocondrial/genética , Perros/clasificación , Variación Genética , Genoma , Masculino , Lobos/clasificación
13.
Immunogenetics ; 70(4): 237-255, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-28951951

RESUMEN

The current information on the polymorphism variation and haplotype structure of the domestic dog leukocyte antigen (DLA) genes is limited in comparison to other experimental animals. In this paper, to better elucidate the degree and types of polymorphisms and genetic differences for DLA-88, DLA-12 and DLA-64, we genotyped four families of 38 beagles and another 404 unrelated dogs representing 49 breeds by RT-PCR based Sanger sequencing. We also sequenced and analyzed the genomic organization of the DLA-88 and DLA-12 gene segments to better define these two-gene DLA haplotypes more precisely. We identified 45 alleles for DLA-88, 15 for DLA-12 and six for DLA-64, of which 20, 14 and six, respectively, were newly described alleles. Therefore, this study shows that the DLA-12 and DLA-64 loci are far more polymorphic than previously reported. Phylogenetic analysis strongly supported that the DLA-88, DLA-12 and DLA-64 alleles were independently generated after the original divergence of the DLA-79 alleles. Two distinct DLA-88 and DLA-12 haplotype structures, tentatively named DLA-88-DLA-12 and DLA-88-DLA-88L, were identified, and the novel haplotype DLA-88-DLA-88L contributed to 32.7% of the unrelated dogs. Quantitative real-time PCR analysis showed that the gene expression levels of DLA-88L and DLA-88 were similar, and that the gene expression level of DLA-12 was significantly lower. In addition, haplotype frequency estimations using frequently occurring alleles revealed 45 different DLA-class I haplotypes (88-88L/12-64) overall, and 22 different DLA-class I haplotypes in homozygous dogs for 18 breeds and mongrels.


Asunto(s)
Perros/genética , Haplotipos , Antígenos de Histocompatibilidad Clase I/genética , Polimorfismo Genético , Alelos , Animales , Cruzamiento , Perros/clasificación , Frecuencia de los Genes , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Antígenos de Histocompatibilidad Clase I/clasificación , Filogenia , Especificidad de la Especie
14.
Immunogenetics ; 70(4): 223-236, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-28924718

RESUMEN

Dogs are an excellent model for human disease. For example, the treatment of canine lymphoma has been predictive of the human response to that treatment. However, an incomplete picture of canine (Canis lupus familiaris) immunoglobulin (IG) and T cell receptor (TR)-or antigen receptor (AR)-gene loci has restricted their utility. This work advances the annotation of the canine AR loci and looks into breed-specific features of the loci. Bioinformatic analysis of unbiased RNA sequence data was used to complete the annotation of the canine AR genes. This annotation was used to query 107 whole genome sequences from 19 breeds and identified over 5500 alleles across the 550 genes of the seven AR loci: the IG heavy, kappa, and lambda loci; and the TR alpha, beta, gamma, and delta loci. Of note was the discovery that half of the IGK variable (V) genes were located downstream of, and inverted with respect to, the rest of the locus. Analysis of the germline sequences of all the AR V genes identified greater conservation between dog and human than mouse with either. This work brings our understanding of the genetic diversity and expression of AR in dogs to the same completeness as that of mice and men, making it the third species to have all AR loci comprehensively and accurately annotated. The large number of germline sequences serves as a reference for future studies, and has allowed statistically powerful conclusions to be drawn on the pressures that have shaped these loci.


Asunto(s)
Perros/genética , Evolución Molecular , Inmunoglobulinas/genética , Receptores de Antígenos de Linfocitos T/genética , Alelos , Animales , Biología Computacional/métodos , Perros/clasificación , Femenino , Frecuencia de los Genes , Humanos , Inmunoglobulinas/clasificación , Masculino , Ratones , Anotación de Secuencia Molecular , Filogenia , Receptores de Antígenos de Linfocitos T/clasificación , Especificidad de la Especie
15.
Biol Lett ; 14(10)2018 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-30333260

RESUMEN

Near Eastern Neolithic farmers introduced several species of domestic plants and animals as they dispersed into Europe. Dogs were the only domestic species present in both Europe and the Near East prior to the Neolithic. Here, we assessed whether early Near Eastern dogs possessed a unique mitochondrial lineage that differentiated them from Mesolithic European populations. We then analysed mitochondrial DNA sequences from 99 ancient European and Near Eastern dogs spanning the Upper Palaeolithic to the Bronze Age to assess if incoming farmers brought Near Eastern dogs with them, or instead primarily adopted indigenous European dogs after they arrived. Our results show that European pre-Neolithic dogs all possessed the mitochondrial haplogroup C, and that the Neolithic and Post-Neolithic dogs associated with farmers from Southeastern Europe mainly possessed haplogroup D. Thus, the appearance of haplogroup D most probably resulted from the dissemination of dogs from the Near East into Europe. In Western and Northern Europe, the turnover is incomplete and haplogroup C persists well into the Chalcolithic at least. These results suggest that dogs were an integral component of the Neolithic farming package and a mitochondrial lineage associated with the Near East was introduced into Europe alongside pigs, cows, sheep and goats. It got diluted into the native dog population when reaching the Western and Northern margins of Europe.


Asunto(s)
Arqueología , ADN Mitocondrial , Perros/genética , Agricultura , Animales , Perros/clasificación , Europa (Continente) , Fósiles , Haplotipos , Humanos , Análisis de Secuencia de ADN
16.
Anim Genet ; 49(1): 94-97, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29349785

RESUMEN

Coat colour dilution may be the result of altered melanosome transport in melanocytes. Loss-of-function variants in the melanophilin gene (MLPH) cause a recessively inherited form of coat colour dilution in many mammalian and avian species including the dog. MLPH corresponds to the D locus in many domestic animals, and recessive alleles at this locus are frequently denoted with d. In this study, we investigated dilute coloured Chow Chows whose coat colour could not be explained by their genotype at the previously known MLPH:c.-22G>A variant. Whole genome sequencing of such a dilute Chow Chow revealed another variant in the MLPH gene: MLPH:c.705G>C. We propose to designate the corresponding mutant alleles at these two variants d1 and d2 . We performed an association study in a cohort of 15 dilute and 28 non-dilute Chow Chows. The dilute dogs were all either compound heterozygous d1 /d2 or homozygous d2 /d2 , whereas the non-dilute dogs carried at least one wildtype allele D. The d2 allele did not occur in 417 dogs from diverse other breeds. However, when we genotyped a Sloughi family, in which a dilute coloured puppy had been born out of non-dilute parents, we again observed perfect co-segregation of the newly discovered d2 allele with coat colour dilution. Finally, we identified a blue Thai Ridgeback with the d1 /d2 genotype. Thus, our data identify the MLPH:c.705G>C as a variant explaining a second canine dilution allele. Although relatively rare overall, this d2 allele is segregating in at least three dog breeds, Chow Chows, Sloughis and Thai Ridgebacks.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Perros/clasificación , Perros/genética , Variación Genética , Pigmentación , Animales , Perros/anatomía & histología
17.
Anim Genet ; 49(5): 492-495, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30062735

RESUMEN

Reliable incidence measurement of diseases is necessary for identification of hereditary diseases in companion animal populations. The data collection system 'PETscan' was developed to facilitate standardized registration of diagnoses in veterinary practice. In the development, we attempted to counter challenges known from other primary practice data systems. PETscan includes a comprehensive list of potential diagnoses and supports the veterinary professionals in the diagnostic process. Demographics, individual data and standardized diagnostic data are collected through practice management software in a central database for epidemiological analysis. A preliminary data analysis from PETscan showed specific health issues in four canine breeds. As a real-time prospective monitoring tool, PETscan summaries can objectively assess the incidence of disorders in companion animal populations and can be used to prioritize disease-gene identification studies and evaluate the effects of breeding strategies, for example, after implementation of a new DNA test in the breeding strategy.


Asunto(s)
Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/epidemiología , Tomografía de Emisión de Positrones/veterinaria , Animales , Enfermedades de los Perros/genética , Enfermedades de los Perros/patología , Perros/clasificación , Perros/genética , Incidencia , Mascotas , Veterinarios
18.
BMC Vet Res ; 13(1): 364, 2017 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-29187176

RESUMEN

BACKGROUND: The prevalence of dog erythrocyte antigen (DEA 1) in canine population is approximately 40-60%. Often data are limited to a small number of breeds and/or dogs. The aims of this study were to evaluate frequency of DEA 1 in a large population of purebred and mongrel dogs including Italian native breeds and to recognize a possible association between DEA 1 and breed, sex, and genetic and phenotypical/functional classifications of breeds. Frequencies of DEA 1 blood group collected from screened/enrolled blood donors and from healthy and sick dogs were retrospectively evaluated. The breed and the sex were recorded when available. DEA 1 blood typing was assessed by immunocromatographic test on K3EDTA blood samples. The prevalence of DEA 1 antigen was statistically related to breed, gender, Fédération Cynologique Internationale (FCI) and genotypic grouping. RESULTS: Sixty-two per cent dogs resulted DEA 1+ and 38% DEA 1-. DEA 1- was statistically associated with Dogo Argentino, Dobermann, German Shepherd, Boxer, Corso dogs, the molossian dogs, the FCI group 1, 2 and 3 and the genetic groups "working dogs" and "mastiff". DEA 1+ was statistically associated with Rottweiler, Briquet Griffon Vendéen, Bernese mountain dog, Golden Retriever, the hunting breeds, the FCI group 4, 6, 7 and 8 and the genetic groups "scent hounds" and "retrievers". No gender association was observed. CONCLUSIONS: Data obtained by this work may be clinically useful to drive blood donor enrollment and selection among different breeds.


Asunto(s)
Antígenos de Grupos Sanguíneos/sangre , Tipificación y Pruebas Cruzadas Sanguíneas/veterinaria , Perros/sangre , Animales , Antígenos de Grupos Sanguíneos/clasificación , Tipificación y Pruebas Cruzadas Sanguíneas/clasificación , Perros/clasificación , Eritrocitos/inmunología , Femenino , Italia/epidemiología , Masculino , Prevalencia , Estudios Retrospectivos , Especificidad de la Especie
19.
J Anim Breed Genet ; 134(2): 144-151, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27488613

RESUMEN

The aim of this study was to evaluate the quality of the data provided from sheepdog trials in Norway, estimate heritabilities, repeatabilities and genetic correlations for the traits included in the trial and make recommendations on how sheepdog trials best can be utilized in the breeding of Border Collies in Norway. The analyses were based on test results from sheepdog trials carried out in Norway from 1993 to 2012. A total of 45 732 records from 3841 Border Collies were available, but after quality assurance only a third was left. The results demonstrated little information in the data. Heritabilities varied between 0.010 and 0.056 with standard errors ranging from 0.010 to 0.023, while repeatabilities ranged from 0.041 to 0.286. There is a need to assure the quality of data to improve the information in the test results. We recommend adding new traits based on the Herding Trait Characterization scheme evaluated in Sweden, and on traits from the predatory motor pattern, regarded as common for all dogs. These new traits may be scored across the elements that make up the current trial system, which should be kept in place to stimulate participation in the genetic evaluation scheme.


Asunto(s)
Cruzamiento , Perros/genética , Perros/fisiología , Animales , Perros/clasificación , Femenino , Masculino , Noruega , Linaje , Conducta Predatoria , Suecia
20.
J Anim Breed Genet ; 134(2): 152-161, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27862377

RESUMEN

Merging pedigree databases across countries may improve the ability of kennel organizations to monitor genetic variability and health-related issues of pedigree dogs. We used data provided by the Société Centrale Canine (France), Svenska Kennelklubben (Sweden) and the Kennel Club (UK) to study the feasibility of merging pedigree databases across countries and describe breeding practices and international gene flow within the following four breeds: Bullmastiff (BMA), English setter (ESE), Bernese mountain dog (BMD) and Labrador retriever (LBR). After merging the databases, genealogical parameters and founder contributions were calculated according to the birth period, breed and registration country of the dogs. Throughout the investigated period, mating between close relatives, measured as the proportion of inbred individuals (considering only two generations of pedigree), decreased or remained stable, with the exception of LBR in France. Gene flow between countries became more frequent, and the origins of populations within countries became more diverse over time. In conclusion, the potential to reduce inbreeding within purebred dog populations through exchanging breeding animals across countries was confirmed by an improved effective population size when merging populations from different countries.


Asunto(s)
Perros/clasificación , Perros/genética , Animales , Evolución Biológica , Cruzamiento , Bases de Datos Genéticas , Perros/fisiología , Femenino , Francia , Masculino , Linaje , Suecia , Reino Unido
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