RESUMO
The German Shepherd Dog (GSD) is a popular working and companion breed for which over 50 hereditary diseases have been documented. Herein, SNP profiles for 197 GSDs were generated using the Affymetrix v2 canine SNP array for a genome-wide association study to identify loci associated with four diseases: pituitary dwarfism, degenerative myelopathy (DM), congenital megaesophagus (ME), and pancreatic acinar atrophy (PAA). A locus on Chr 9 is strongly associated with pituitary dwarfism and is proximal to a plausible candidate gene, LHX3. Results for DM confirm a major locus encompassing SOD1, in which an associated point mutation was previously identified, but do not suggest modifier loci. Several SNPs on Chr 12 are associated with ME and a 4.7 Mb haplotype block is present in affected dogs. Analysis of additional ME cases for a SNP within the haplotype provides further support for this association. Results for PAA indicate more complex genetic underpinnings. Several regions on multiple chromosomes reach genome-wide significance. However, no major locus is apparent and only two associated haplotype blocks, on Chrs 7 and 12 are observed. These data suggest that PAA may be governed by multiple loci with small effects, or it may be a heterogeneous disorder.
Assuntos
Doenças do Cão/genética , Nanismo Hipofisário/veterinária , Acalasia Esofágica/veterinária , Estudo de Associação Genômica Ampla/veterinária , Pancreatopatias/veterinária , Doenças da Medula Espinal/veterinária , Animais , Mapeamento Cromossômico , Cães , Nanismo Hipofisário/genética , Acalasia Esofágica/genética , Predisposição Genética para Doença , Genoma , Proteínas com Homeodomínio LIM/genética , Pancreatopatias/genética , Polimorfismo de Nucleotídeo Único , Doenças da Medula Espinal/genética , Superóxido Dismutase/genética , Superóxido Dismutase-1 , Fatores de Transcrição/genéticaRESUMO
Harlequin is a pigmentary trait of the domestic dog that is controlled by two autosomal loci: the melanosomal gene, SILV, and a modifier gene, harlequin (H), previously localized to chromosome 9. Heterozygosity for a retrotransposon insertion in SILV and a mutation in H causes a pattern of black patches on a white background. Homozygosity for H is embryonic lethal. Fine mapping of the harlequin locus revealed a 25 kb interval wherein all harlequin Great Danes are heterozygous for a common haplotype. This region contains one gene, PSMB7, which encodes the ß2 catalytic subunit of the proteasome. Sequence analysis identified a coding variant in exon 2 that segregates with harlequin patterning. The substitution predicts the replacement of a highly conserved valine with a glycine. Described herein is the identification of a naturally-occurring mutation of the ubiquitin proteasome system that is associated with a discernable phenotype of dogs.
Assuntos
Cães/anatomia & histologia , Cães/genética , Cor de Cabelo/genética , Mutação de Sentido Incorreto , Complexo de Endopeptidases do Proteassoma/genética , Sequência de Aminoácidos , Animais , Cruzamento , Mapeamento Cromossômico , Haplótipos , Heterozigoto , Homozigoto , Dados de Sequência Molecular , Fenótipo , Retroelementos/genética , Análise de Sequência de DNA , Antígeno gp100 de Melanoma/genéticaRESUMO
The domestic dog is of great benefit to humankind, not only through companionship and working activities cultivated through domestication and selective breeding, but also as a model for biomedical research. Many single-gene traits have been well-characterized at the genomic level, and recent advances in whole-genome association studies will allow for better understanding of complex, multigenic hereditary diseases. Additionally, the dog serves as an invaluable large animal model for assessment of novel therapeutic agents. Thus, the dog has filled a crucial step in the translation of basic research to new treatment regimens for various human diseases. Four well-characterized diseases in canine models are discussed as they relate to other animal model availability, novel therapeutic approach, and extrapolation to human gene therapy trials.
Assuntos
Modelos Animais de Doenças , Cães , Terapia Genética , Animais , Doença/genética , Cães/genética , Humanos , Pesquisa Translacional BiomédicaRESUMO
Naturally occurring cystic fibrosis (CF)-causing mutations in the CFTR gene have not been identified in any nonhuman animal species. Since domestic dogs are known to develop medical conditions associated with atypical CF in humans (e.g., bronchiectasis and pancreatitis), we hypothesized that dogs with these disorders likely have a higher expression rate of CFTR mutations than the at-large population. Temporal temperature-gradient gel electrophoresis (TTGE) was used to screen canine CFTR in 400 animals: 203 dogs diagnosed with pancreatitis, 23 dogs diagnosed with bronchiectasis, and 174 dogs admitted to clinics for any illness (at-large dogs). Twenty-eight dogs were identified with one of four CFTR missense mutations. P1281T and P1464H mutations occur in relatively unconserved residues. R1456W is analogous to the human R1453W mutation, which has approximately 20% of normal CFTR function and is associated with pancreatitis and panbronchiolitis. R812W disrupts a highly conserved protein kinase A recognition site within the regulatory domain. We conclude that naturally occurring CFTR mutations are relatively common in domestic dogs and can be detected with TTGE. No substantive differences in mutation frequency were observed between the at-large, pancreatitis, and bronchiectasis dogs.
Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Cães/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Bronquiectasia/genética , Bronquiectasia/veterinária , Análise Mutacional de DNA , Doenças do Cão/genética , Frequência do Gene , Dados de Sequência Molecular , Mutação/fisiologia , Homologia de Sequência de AminoácidosRESUMO
OBJECTIVE: To elucidate the pathogenesis of Greyhound meningoencephalitis by evaluating gene expression in diseased brain tissue. ANIMALS: Cadavers of 3 diseased (8- to 15-month-old) and 3 (10-month-old) control Greyhounds. PROCEDURES: Samples of RNA were extracted from brain tissue of all dogs and evaluated by use of a canine-specific microarray. RESULTS: A unique profile involving significant alterations in expression of 21 genes was evident in diseased dogs, compared with expression in control dogs. Most genes with up-regulated expression were related to immune function, with the remaining genes involved in ligand binding, signal transduction, transcriptional regulation, and formation and transportation of proteins including enzymes. Of notable involvement were genes encoding for major histocompatibility complexes, small inducible cytokine A5 precursor, myxovirus-resistant proteins, and components of the classical complement pathway, which are all genes common to pathways of viral infections and autoimmunity. CONCLUSIONS AND CLINICAL RELEVANCE: Although results of microarray analysis did not clearly define a potential etiology of Greyhound meningoencephalitis, they did highlight a consistent gene alteration signature that would suggest a common etiology and pathogenesis for this condition.
Assuntos
Encéfalo/fisiopatologia , Doenças do Cão/genética , Meningoencefalite/genética , Meningoencefalite/veterinária , Animais , Cães , Enzimas/genética , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Masculino , Proteínas do Tecido Nervoso/genética , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase , Valores de ReferênciaRESUMO
Necrotizing meningoencephalitis (NME) in the Pug is an invariably fatal disease with an early age of onset whose cause remains unknown. Breed predilection strongly suggests genetic component(s), and viral etiology proves negative in studied cases. The current study was undertaken as the first analysis of the heritable component(s) involved in NME in the Pug. Complete medical records, individual characteristics, and pedigree information were collected for 58 affected dogs with data pertaining to 4698 dogs analyzed. A high inbreeding coefficient with differences across gender and significant differences across coat color classes and variable expression was evident. Median onset age was 19months and median survival time 23days. Screening for herpes-, adeno-, and parvoviruses was negative. The data demonstrate a strong familial inheritance of NME in the Pug. This investigation provides parameters of disease from the largest Pug NME cohort analyzed to date and offers evidence of previously unrecognized familial inheritance.
Assuntos
Doenças do Cão/genética , Meningoencefalite/genética , Animais , Doenças do Sistema Nervoso Central/genética , Doenças do Sistema Nervoso Central/veterinária , DNA/genética , DNA/isolamento & purificação , Cães , Feminino , Cor de Cabelo/genética , Masculino , Meningoencefalite/mortalidade , Meningoencefalite/veterinária , Fenótipo , Reação em Cadeia da Polimerase , Caracteres Sexuais , Taxa de SobrevidaRESUMO
OBJECTIVE: To identify the quantitative trait loci (QTL) that contribute to hip dysplasia in dogs. ANIMALS: 192 Labrador Retrievers. PROCEDURES: Hip dysplasia was measured by use of the Norberg angle (NA), dorsolateral subluxation (DLS) score, and distraction index (DI). Genome-wide screening was conducted by use of 276 unique microsatellites. Linkage analysis was performed with a variance-based linear model. Logarithm of the odds (LOD) scores were reported when values were > 2.0. RESULTS: Canis familiaris autosomes (CFAs) 01, 02, 10, 20, 22, and 32 harbored significant QTL at LOD scores > 2.0. Among the 6 QTL, the QTL on CFA02 had not been reported to harbor QTL for hip dysplasia. The highest LOD score of 3.32 on CFA20 contributed to the second principal component of the DLS score and NA of the right hip joint. The QTL that was mapped on CFA01 (LOD score of 3.13 at 55 centimorgans) was located on the same chromosome reported to harbor a QTL for hip dysplasia in Portuguese Water Dogs and German Shepherd Dogs. In this study, CFAs 10, 20, 22, and 32 harbored QTL for hip dysplasia that have been identified in a Labrador Retriever-Greyhound pedigree and in German Shepherd Dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Multiple QTL were clearly involved with hip dysplasia. Identification of these QTL will enable fine-resolution mapping and subsequent assessment of candidate genes within the refined intervals to enable researchers to develop genetic screening tests and preventative and novel therapeutic regimens.
Assuntos
Doenças do Cão/genética , Displasia Pélvica Canina/genética , Locos de Características Quantitativas , Animais , DNA/genética , DNA/isolamento & purificação , Cães , Feminino , Genótipo , Articulação do Quadril/patologia , Tamanho da Ninhada de Vivíparos , Masculino , Repetições de Microssatélites/genética , Linhagem , Fenótipo , Especificidade da EspécieRESUMO
Harlequin is a coat pattern of the Great Dane characterized by ragged patches of full color on a white background. Harlequin patterning is a bigenic trait, resulting from the interaction of the merle allele of SILV, and a dominant modifier locus, H. Breeding data suggest that H is embryonic recessive lethal and that all harlequins are Hh. To identify linkage with the harlequin phenotype, 46 Great Danes from 5 pedigrees were genotyped for 280 microsatellite markers in a whole genome screen. One marker on the telomeric end of chromosome 9 was suggestive of linkage. Fine mapping of this region using additional microsatellite markers and 10 Great Danes from a sixth pedigree resulted in significant LOD scores for 2 markers. Reported herein is linkage mapping of the H locus to a 3.27 Mb region of chromosome 9 containing approximately 20 genes.
Assuntos
Mapeamento Cromossômico , Cães/genética , Cor de Cabelo/genética , Animais , Genótipo , Heterozigoto , LinhagemRESUMO
Mutations of pigment type switching have provided basic insight into melanocortin physiology and evolutionary adaptation. In all vertebrates that have been studied to date, two key genes, Agouti and Melanocortin 1 receptor (Mc1r), encode a ligand-receptor system that controls the switch between synthesis of red-yellow pheomelanin vs. black-brown eumelanin. However, in domestic dogs, historical studies based on pedigree and segregation analysis have suggested that the pigment type-switching system is more complicated and fundamentally different from other mammals. Using a genomewide linkage scan on a Labrador x greyhound cross segregating for black, yellow, and brindle coat colors, we demonstrate that pigment type switching is controlled by an additional gene, the K locus. Our results reveal three alleles with a dominance order of black (K(B)) > brindle (k(br)) > yellow (k(y)), whose genetic map position on dog chromosome 16 is distinct from the predicted location of other pigmentation genes. Interaction studies reveal that Mc1r is epistatic to variation at Agouti or K and that the epistatic relationship between Agouti and K depends on the alleles being tested. These findings suggest a molecular model for a new component of the melanocortin signaling pathway and reveal how coat-color patterns and pigmentary diversity have been shaped by recent selection.
Assuntos
Segregação de Cromossomos , Epistasia Genética , Ligação Genética , Cor de Cabelo/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Receptor Tipo 1 de Melanocortina/genética , Proteína Agouti Sinalizadora , Alelos , Animais , Mapeamento Cromossômico , Cromossomos , Cães , Hormônios Estimuladores de Melanócitos/antagonistas & inibidores , Pigmentação/genéticaRESUMO
OBJECTIVE: To identify quantitative trait loci (QTL) associated with osteoarthritis (OA) of hip joints of dogs by use of a whole-genome microsatellite scan. ANIMALS: 116 founder, backcross, F1, and F2 dogs from a crossbred pedigree. PROCEDURES: Necropsy scores and an optimized set of 342 microsatellite markers were used for interval mapping by means of a combined backcross and F2 design module from an online statistical program. Breed and sex were included in the model as fixed effects. Age of dog at necropsy and body weight at 8 months of age were also included in the model as covariates. The chromosomal location at which the highest F score was obtained was considered the best estimate of a QTL position. Chromosome-wide significance thresholds were determined empirically from 10,000 permutations of marker genotypes. RESULTS: 4 chromosomes contained putative QTL for OA of hip joints in dogs at the 5% chromosome-wide significance threshold: chromosomes 5, 18, 23, and 31. CONCLUSIONS AND CLINICAL RELEVANCE: Osteoarthritis of canine hip joints is a complex disease to which many genes and environmental factors contribute. Identification of contributing QTL is a strategy to elucidate the genetic mechanisms that underlie this disease. Refinement of the putative QTL and subsequent candidate gene studies are needed to identify the genes involved in the disease process.
Assuntos
Doenças do Cão/genética , Cães/genética , Osteoartrite/veterinária , Locos de Características Quantitativas , Envelhecimento , Animais , Mapeamento Cromossômico , Cruzamentos Genéticos , Doenças do Cão/patologia , Feminino , Articulação do Quadril/patologia , Masculino , Osteoartrite/genética , Osteoartrite/patologia , Polimorfismo GenéticoRESUMO
Dermatomyositis (DM) is a canine and human inflammatory disease of the skin and muscle that is thought to be autoimmune in nature. In dogs, DM occurs most often in the rough collie and Shetland sheepdog. Characteristic skin lesions typically develop on the face, ears, tail, and distal extremities. The severity of lesions varies and is thought to increase with stressful stimuli. Previous studies in the collie suggest that DM is inherited in an autosomal dominant fashion with incomplete penetrance. The work presented here concerns gene transcripts profiling and immunobiology of DM in the Shetland sheepdog. Gene transcript profiles were generated for affected and normal skin using a canine-specific oligonucleotide array having 49,929 probe sets. Two-hundred and eight-five gene transcripts, many of which are involved in immune function, were found to be differentially regulated in these tissues. Also reported are Western blot, immunohistochemistry, and immunofluorescence analyses which showed that staining patterns with sera from normal and affected dogs are quite similar. While our work suggests that canine DM is a disease that may be immune mediated, it did not detect the production of specific disease-associated autoantibodies.
Assuntos
Dermatomiosite/veterinária , Doenças do Cão/genética , Perfilação da Expressão Gênica/veterinária , Análise de Sequência com Séries de Oligonucleotídeos/veterinária , Animais , Western Blotting/veterinária , Dermatomiosite/genética , Dermatomiosite/imunologia , Dermatomiosite/patologia , Doenças do Cão/imunologia , Doenças do Cão/patologia , Cães , Feminino , Imuno-Histoquímica/veterinária , Masculino , Linhagem , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterináriaRESUMO
Recently, a novel group of genes encoding small RNA molecules, termed microRNAs (miRNAs), has been discovered to play a vital role in eukaryotic gene expression. Known to act in a post-transcriptional fashion, miRNAs can inhibit translation by binding to messenger RNA (mRNA) or by targeting mRNA for degradation. A search of genetic databases revealed significant conservation of miRNA genes between the domestic dog and the human. This finding suggests that expression patterns may also be conserved. Proof of principle experiments, including serial dilutions and sequencing, were performed to verify that primers made to amplify human mature miRNAs can be used to amplify canine miRNAs, providing that the mature sequences are conserved. TaqMan Real-time PCR techniques were used to isolate the first miRNA mature products from canine tissues. The expression levels of miR-17-3p, miR-17-5p, miR-18, miR-19a, miR-19b, miR-20, and miR-92 were evaluated in five canine tissues (heart, lung, brain, kidney, and liver) using the delta-delta Ct (critical threshold) method.
Assuntos
Cães/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Humanos , MicroRNAs/análise , Técnicas de Amplificação de Ácido Nucleico , Análise de Sequência de RNA , Distribuição TecidualRESUMO
Primary Sertoli cell cultures have been established from several animals including the sheep and rhesus monkey; however, not for the domestic dog, Canis familiaris. Sertoli cells are the only readily accessible cell type in the body which expresses all six type IV collagens. These collagens play key roles in tissue structure, basement membrane formation, and filtration. The study of these genes is necessary to determine their exact roles and regulation in the aforementioned functions and to investigate diseases associated with mutations in these genes. For such studies, a cell culture system is a requisite tool. Therefore, Sertoli cells were targeted, and a culture was established from cells isolated from canine testes. Cultures maintained consistent morphology and steady growth for up to seven passages. Cultured cells were identified as Sertoli cells through positive Western blot results for SOX9 and Clusterin B proteins and transcript sequence verification of SOX9 as well as the presence of type IV collagen transcripts. Primary cultures of canine Sertoli cells will provide a useful tool for study of the function and regulation of collagen genes and will permit new research pertaining to canine health while also serving as a model for the study of human diseases.
Assuntos
Técnicas de Cultura de Células/métodos , Cães , Células de Sertoli/citologia , Animais , Separação Celular , Células Cultivadas , Colágeno Tipo IV/metabolismo , Dimerização , Proteínas de Grupo de Alta Mobilidade/metabolismo , Masculino , Fatores de Transcrição SOX9 , Fatores de Transcrição/metabolismoRESUMO
This study was undertaken to determine the association between life spans and breed size in the dog, based upon data derived from the pet population. Seventy-seven American Kennel Club breeds were analyzed with data collected for more than 700 dogs. Multiple linear regression analysis was carried out with longevity as the dependent variable and height or weight as the independent variable. A negative correlation was observed between height and longevity (r=-0.603, p<0.05), and between weight and longevity (r=-0.679, p<0.05). Weight was the significant predictor of life span (p<0.001), revealing that breeds smaller by weight generally live longer than heavier breeds. These data form the ground work for investigations of aging utilizing the dog as a model and provide owners with a quantitative method for predicting lifespan of dog breeds, thereby aiding in pet selection.
Assuntos
Peso Corporal/fisiologia , Cães/fisiologia , Longevidade/fisiologia , Animais , Cães/crescimento & desenvolvimento , Feminino , MasculinoRESUMO
BACKGROUND: Autosomal recessive hereditary nephropathy (ARHN) in the English Cocker Spaniel is caused by a type IV collagen defect, but the underlying mutation is unknown. ANIMALS: One hundred thirty-four English Cocker Spaniels (12 with ARHN, 8 obligate carriers, and 114 others), 3 mixed breed dogs with X-linked hereditary nephropathy (XLHN), and 7 other dogs without hereditary nephropathy were included. METHODS: Diagnosis of ARHN was based on transmission electron microscopy and immunostaining of kidney. Quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR) was used to compare COL4A3, COL4A4, and COL4A5 mRNA concentrations in the renal cortex from ARHN-affected English Cocker Spaniels, XLHN-affected dogs, and dogs without hereditary nephropathy. The entire coding region of COL4A4 was sequenced in 2 ARHN-affected dogs, 2 obligate carriers, 2 English Cocker Spaniels of unknown status, and 2 healthy mixed breed dogs. The exon containing the mutation was sequenced for all 134 English Cocker Spaniels. RESULTS: Quantitative real time RT-PCR implicated COL4A4 as the gene harboring the mutation, and sequencing identified a single nucleotide substitution at base 115 as the cause of ARHN in English Cocker Spaniels. This mutation, which causes a premature stop codon in exon 3 of COL4A4, was segregated with clinical status in all affected dogs and obligate carriers. The mutation also was identified in 39 of 114 other English Cocker Spaniels with previously unknown status. CONCLUSIONS AND CLINICAL IMPORTANCE: The cause of this disease has been identified, and use of a test for the mutation will permit eradication of ARHN in the English Cocker Spaniel.
Assuntos
Doenças do Cão/genética , Doenças Genéticas Ligadas ao Cromossomo X/veterinária , Imuno-Histoquímica/veterinária , Nefropatias/veterinária , Rim/ultraestrutura , Animais , Sequência de Bases , Diagnóstico Diferencial , Doenças do Cão/diagnóstico , Doenças do Cão/patologia , Cães , Éxons , Feminino , Rim/patologia , Nefropatias/diagnóstico , Nefropatias/genética , Nefropatias/patologia , Masculino , Dados de Sequência Molecular , Mutação , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterináriaRESUMO
Canine hip dysplasia (CHD) is characterized by a malformation of the hip joint that leads to joint laxity and consequential degenerative joint disease. The most widely used method for diagnosis of CHD is the ventrodorsal hip-extended radiologic view, commonly referred to as the Orthopedic Foundation for Animals (OFA) method. The method of the University of Pennsylvania Hip Improvement Program (PennHIP), an alternative technique that is based on hip joint laxity, provides a quantitative assessment, the distraction index (DI), of the likelihood of the development of CHD because of increased laxity in the hip joint. Linear regression analysis showed that, across many breeds of dog, the incidence of CHD, as defined by the OFA, is positively correlated with the mean DI, the determination coefficient (r2) being 26%. We used families of Boykin spaniels (BSs) to determine the level of joint laxity in the breed and to conduct an initial whole-genome screening to identify markers that co-segregate with increased joint laxity. Although there was a positive correlation between the incidence of hip dysplasia and increased joint laxity, we did not find significant linkage in the 28 BSs that underwent genotyping, likely owing to the small size of the pedigree.
Assuntos
Marcadores Genéticos , Displasia Pélvica Canina/genética , Animais , Peso Corporal/fisiologia , Cães , Feminino , Genótipo , Displasia Pélvica Canina/epidemiologia , Incidência , Masculino , LinhagemRESUMO
BACKGROUND: The distinctive coat pattern of a Dalmatian is the result of the interaction of several loci. While the encoded function of these genes is not fully understood, it is known the Piebald, Ticking, and Flecking loci interact to produce the Dalmatian's classic pigmented spots on a white background. The color of the pigmented spots in purebred Dalmatians can either be black or liver, but the locus responsible for color determination is unknown. Studies have been conducted to determine the underlying genes involved in coat color determination in the dog, e.g., in the Labrador Retriever, but none to date have addressed black versus liver in the Dalmatian. RESULTS: A genome scan was conducted in a multi-generational kindred of Dalmatians segregating black and liver spot color. Linkage analysis was performed using a total of 113 polymorphic microsatellite markers from the kindred. Linkage was found between spot color and a single microsatellite marker, FH2319 (LOD = 12.5) on chromosome 11. CONCLUSION: The TYRP1 (Brown) locus is located at position 50.1 Mb on chromosome 11, which is approximately 0.4 Mb from marker FH2319. Given the recent characterization of TYRP1 genetic variations in the dog and the linkage evidence reported here, TYRP1 is likely responsible for the spot color variation of black versus liver seen in the Dalmatian.
RESUMO
OBJECTIVE: To identify microsatellite markers linked to progressive retinal atrophy (PRA) in American Eskimo Dogs. SAMPLE POPULATION: Blood samples or buccal epithelial cells from 66 American Eskimo Dogs, including 53 PRA-unaffected and 13 PRA-affected dogs. PROCEDURE: The genotypes of unaffected and affected dogs were determined by use of microsatellite markers spanning canine chromosome 9 (CFA09). Homozygosity mapping was used to detect linkage between markers and the gene locus for PRA. RESULTS: Significant allelic association between marker alleles and the gene locus for PRA was detected for GALK1 and TK1, indicating linkage between these markers and the causative gene locus for PRA. CONCLUSIONS AND CLINICAL RELEVANCE: These data indicate that PRA in American Eskimo Dogs is located on CFA09 and allow for the development of a microsatellite-based test to identify carrier (unaffected) and affected dogs before clinical signs appear.
Assuntos
Doenças do Cão/genética , Oftalmopatias Hereditárias/veterinária , Repetições de Microssatélites/genética , Doenças Retinianas/veterinária , Alelos , Animais , Mapeamento Cromossômico/veterinária , DNA/química , DNA/genética , Cães , Oftalmopatias Hereditárias/genética , Feminino , Genótipo , Masculino , Reação em Cadeia da Polimerase/veterinária , Doenças Retinianas/genéticaRESUMO
Although recent endeavors to discover the mechanisms of the aging process have been numerous and successful, there is still much to be learned. Genes implicated in the aging process were mapped to the canine genome and will serve as additional framework markers for the assignment of contiguous segments from the canine genome sequence to chromosomes. The 54 genes were selected because of their demonstrated contribution to longevity in other organisms or based upon their proximity to a marker, D4S1564, on human chromosome 4 (Puca et al., 2001). This effort lays the necessary groundwork for our utilization of the domestic dog as a model organism to define the genes that govern aging and longevity. Within the species, naturally diverse life expectancies and highly homogeneous populations create an ideal population structure for studying the genetic components of aging (Patronek et al., 1997).
Assuntos
Envelhecimento/genética , Genes , Animais , Cromossomos Humanos Par 4 , Cromossomos de Mamíferos , Cães , Humanos , Modelos Animais , Mapeamento de Híbridos RadioativosRESUMO
Our interest is in understanding the genetic bases for hereditary renal diseases of the domestic dog (Canis familiaris) and in characterizing gene loci for placement on the map of the canine genome. We report here on the cloning, sequencing and radiation hybrid mapping of the canine cDNA encoding uromodulin, a renal-specific glycoprotein. The cDNA is 2.3 kb in length and, as expected, comparisons of nucleotide sequences reveal that canine umod is quite similar to umod of other mammals. The predicted amino acid sequence of canine uromodulin has at least 70% identity with other mammalian uromodulin proteins. Canine umod has been mapped on the RHDF5000 radiation hybrid panel and positioned on the most recent canine genome map. Data indicate that umod is linked to the marker CZP2 (canine zona pellucida gene) on an RH group not yet assigned to a canine chromosome. The human umod and CZP2 genes are located on chromosome 16p13.