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Jan Rothuizen - One of the best experts on this subject based on the ideXlab platform.
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Disease burden in four populations of Dog and cat breeds compared to mixed-breed Dogs and European shorthair cats.
Preventive veterinary medicine, 2017Co-Authors: S. F. A. Keijser, Peter A.j. Leegwater, Hille Fieten, Jan Rothuizen, L.e. Meijndert, B.j. Carrière, F.g. Van Steenbeek, Mirjam NielenAbstract:Current public and professional opinion is that many Dog breeds suffer from health issues related to inherited diseases or extreme phenotypes. The aim of this historical comparative observational study was to evaluate the breed-related disease burden in three Purebred Dog populations (Chihuahua, French bullDog, Labrador retriever) and one Purebred cat breed (Persian cats) in the Netherlands by comparison to a control population of mixed-breed Dogs and European Shorthair cats. A qualitative query was performed, consisting of a literature review and collecting the expert opinions of University veterinary specialists, to gather insight into potential diseases of the study population. Next, a referral clinic case control study of the patients referred to specific medical disciplines in the University Clinic was performed. The odds ratio (OR) was calculated to determine the likelihood of a patient referred to a particular medical discipline being a certain breed. Together, the qualitative query and the case control study resulted in a list of potentially relevant diseases limited to five organ systems per breed. These were analysed in data from primary practices. Patient files from ten primary practices over a period of two years were manually extracted and examined. Four-hundred individual patient records per breed as well as 1000 non-breed records were randomly selected from the 10 practices, weighted per practice size. Records were then examined and the presence or absence of certain diseases was identified. To evaluate the disease burden per breed, proportional difference (PD) was estimated, as well as the animal's age at presentation in months. The results of the referral clinic case control study showed an overrepresentation (Odds Ratio>1.5) of the selected breeds in several medical specialties, while median age at presentation was in some cases significantly lower than in the non-breed animals. Results of the practice-based extended cross-sectional study showed that only a few of the selected diseases contribute to the disease burden in these Purebred populations, which was different from the expectations derived from the literature or expert opinion. Additional results included age difference at presentation, which may be interpreted as age of onset, and could indicate a higher disease burden for the individual animal. Also, only a small percentage of Purebred Dogs was registered with the national kennel club. Our final recommendation is that population-based data mining is needed to evaluate country-specific companion animal health and welfare.
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New canine models of copper toxicosis: diagnosis, treatment, and genetics
Annals of the New York Academy of Sciences, 2014Co-Authors: Hille Fieten, Peter A.j. Leegwater, Louis C. Penning, Jan RothuizenAbstract:The One Health principle recognizes that human health, animal health, and environmental health are inextricably linked. An excellent example is the study of naturally occurring copper toxicosis in Dogs to help understand human disorders of copper metabolism. Besides the Bedlington terrier, where copper toxicosis is caused by a mutation in the COMMD1 gene, more complex hereditary forms of copper-associated hepatitis were recognized recently in other Dog breeds. The Labrador retriever is one such breed, where an interplay between genetic susceptibility and exposure to copper lead to clinical copper toxicosis. Purebred Dog populations are ideal for gene mapping studies, and because genes involved in copper metabolism are highly conserved across species, newly identified gene mutations in the Dog may help unravel the genetic complexity of different human forms of copper toxicosis. Furthermore, increasing knowledge with respect to diagnosis and treatment strategies will benefit both species.
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Distribution of extrahepatic congenital portosystemic shunt morphology in predisposed Dog breeds
BMC Veterinary Research, 2012Co-Authors: Lindsay Van Den Bossche, Peter A.j. Leegwater, Frank G Van Steenbeek, Robert P Favier, Anne Kummeling, Jan RothuizenAbstract:Background An inherited basis for congenital extrahepatic portosystemic shunts (EHPSS) has been demonstrated in several small Dog breeds. If in general both portocaval and porto-azygous shunts occur in breeds predisposed to portosystemic shunts then this could indicate a common genetic background. This study was performed to determine the distribution of extrahepatic portocaval and porto-azygous shunts in Purebred Dog populations. Results Data of 135 client owned Dogs diagnosed with EHPSS at the Faculty of Veterinary Medicine of Utrecht University from 2001 – 2010 were retrospectively analyzed. The correlation between shunt localization, sex, age, Dog size and breed were studied. The study group consisted of 54 males and 81 females from 24 breeds. Twenty-five percent of Dogs had porto-azygous shunts and 75% had portocaval shunts. Of the Dogs with porto-azygous shunts only 27% was male ( P = 0.006). No significant sex difference was detected in Dogs with a portocaval shunt. Both phenotypes were present in almost all breeds represented with more than six cases. Small Dogs are mostly diagnosed with portocaval shunts (79%) whereas both types are detected. The age at diagnosis in Dogs with porto-azygous shunts was significantly higher than that of Dogs with portocaval shunts ( P
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canine models of copper toxicosis for understanding mammalian copper metabolism
Mammalian Genome, 2012Co-Authors: Hille Fieten, Peter A.j. Leegwater, Adrian Watson, Jan RothuizenAbstract:Hereditary forms of copper toxicosis exist in man and Dogs. In man, Wilson’s disease is the best studied disorder of copper overload, resulting from mutations in the gene coding for the copper transporter ATP7B. Forms of copper toxicosis for which no causal gene is known yet are recognized as well, often in young children. Although advances have been made in unraveling the genetic background of disorders of copper metabolism in man, many questions regarding disease mechanisms and copper homeostasis remain unanswered. Genetic studies in the Bedlington terrier, a Dog breed affected with copper toxicosis, identified COMMD1, a gene that was previously unknown to be involved in copper metabolism. Besides the Bedlington terrier, a number of other Dog breeds suffer from hereditary copper toxicosis and show similar phenotypes to humans with copper storage disorders. Unlike the heterogeneity of most human populations, the genetic structure within a Purebred Dog population is homogeneous, which is advantageous for unraveling the molecular genetics of complex diseases. This article reviews the work that has been done on the Bedlington terrier, summarizes what was learned from studies into COMMD1 function, describes hereditary copper toxicosis phenotypes in other Dog breeds, and discusses the opportunities for genome-wide association studies on copper toxicosis in the Dog to contribute to the understanding of mammalian copper metabolism and copper metabolism disorders in man.
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Relationship of cryptorchidism with sex ratios and litter sizes in 12 Dog breeds
Animal Reproduction Science, 2008Co-Authors: Ed J. Gubbels, Janneke Scholten, Luc Janss, Jan RothuizenAbstract:The aim of this study was to identify the influence of genetic carriership for cryptorchidism on litter sizes and sex ratios in the offspring. Weaning data of 11,230 litters in 12 Purebred Dog breeds were evaluated. Parents were classified as cryptorchidism ‘carriers’ (C) when at least one of their offspring was found cryptorchid. Subsequently the effects of ‘carrier’ and ‘non-carrier’ (NC) parents on their litters were studied. In litters from C × C parents we found an increased number of males per litter in all breeds, a reduced number of females per litter in 8 breeds and an increased litter size in 11 breeds in comparison with litters from NC × NC parents. Over all breeds the effects on litter size, on number of males per litter and on sex ratio were highly significant. Mixed litters from C × NC and NC × C did not show these effects and were not significantly different from the NC × NC offspring. Our results suggest a general mechanism in the Dog species which causes cryptorchidism as well as increased male/female ratios and increased litter sizes. A consequence of such a mechanism is that selection in favor of increasing reproduction output frustrates selective efforts to eliminate cryptorchidism.
Elaine A Ostrander - One of the best experts on this subject based on the ideXlab platform.
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A genetic dissection of breed composition and performance enhancement in the Alaskan sled Dog
BMC Genetics, 2010Co-Authors: Heather J Huson, Heidi G Parker, Jonathan Runstadler, Elaine A OstranderAbstract:Background The Alaskan sled Dog offers a rare opportunity to investigate the development of a Dog breed based solely on performance, rather than appearance, thus setting the breed apart from most others. Several established breeds, many of which are recognized by the American Kennel Club (AKC), have been introduced into the sled Dog population to enhance racing performance. We have used molecular methods to ascertain the constitutive breeds used to develop successful sled Dog lines, and in doing so, determined the breed origins of specific performance-related behaviors. One hundred and ninety-nine Alaskan sled Dogs were genotyped using 96 microsatellite markers that span the canine genome. These data were compared to that from 141 similarly genotyped Purebred Dog breeds. Sled Dogs were evaluated for breed composition based on a variety of performance phenotypes including speed, endurance and work ethic, and the data stratified based on population structure. Results We observe that the Alaskan sled Dog has a unique molecular signature and that the genetic profile is sufficient for identifying Dogs bred for sprint versus distance. When evaluating contributions of existing breeds we find that the Alaskan Malamute and Siberian Husky contributions are associated with enhanced endurance; Pointer and Saluki are associated with enhanced speed and the Anatolian Shepherd demonstrates a positive influence on work ethic. Conclusion We have established a genetic breed profile for the Alaskan sled Dog, identified profile variance between sprint and distance Dogs, and established breeds associated with enhanced performance attributes. These data set the stage for mapping studies aimed at finding genes that are associated with athletic attributes integral to the high performing Alaskan sled Dog.
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a genetic dissection of breed composition and performance enhancement in the alaskan sled Dog
BMC Genetics, 2010Co-Authors: Heidi G Parker, Jonathan Runstadler, Heather J Huson, Elaine A OstranderAbstract:The Alaskan sled Dog offers a rare opportunity to investigate the development of a Dog breed based solely on performance, rather than appearance, thus setting the breed apart from most others. Several established breeds, many of which are recognized by the American Kennel Club (AKC), have been introduced into the sled Dog population to enhance racing performance. We have used molecular methods to ascertain the constitutive breeds used to develop successful sled Dog lines, and in doing so, determined the breed origins of specific performance-related behaviors. One hundred and ninety-nine Alaskan sled Dogs were genotyped using 96 microsatellite markers that span the canine genome. These data were compared to that from 141 similarly genotyped Purebred Dog breeds. Sled Dogs were evaluated for breed composition based on a variety of performance phenotypes including speed, endurance and work ethic, and the data stratified based on population structure. We observe that the Alaskan sled Dog has a unique molecular signature and that the genetic profile is sufficient for identifying Dogs bred for sprint versus distance. When evaluating contributions of existing breeds we find that the Alaskan Malamute and Siberian Husky contributions are associated with enhanced endurance; Pointer and Saluki are associated with enhanced speed and the Anatolian Shepherd demonstrates a positive influence on work ethic. We have established a genetic breed profile for the Alaskan sled Dog, identified profile variance between sprint and distance Dogs, and established breeds associated with enhanced performance attributes. These data set the stage for mapping studies aimed at finding genes that are associated with athletic attributes integral to the high performing Alaskan sled Dog.
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Human Genetics and the Canine System
Vogel and Motulsky's Human Genetics, 2010Co-Authors: Heidi G Parker, Elaine A OstranderAbstract:With constant advances in canine genomics, the Dog has found a permanent position as a source of genetic information for the inheritance of morphologic traits and disease susceptibility. The modern domestic Dog is not a typical model organism. They share our environment, our life-styles and often our food. In addition, they experience many of the same diseases that people do and are diagnosed and treated using the same medical procedures and pharmaceuticals. However, unlike humans, the Purebred Dog maintains a highly structured population organization that, if used correctly, can simplify the genetics of complex traits and disorders. In this chapter, we will discuss the history of canine genomics along with recent advances in resource development. Specific examples will be provided to demonstrate strategies for using population stratification to the best advantage in mapping traits both simple and complex. Together, these data highlight the utility of the canine system for mapping traits and finding mutations important in both human and companion animal science.
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Understanding the genetics of autoimmune disease: two loci that regulate late onset Addison's disease in Portuguese Water Dogs.
International journal of immunogenetics, 2006Co-Authors: Kevin Chase, Elaine A Ostrander, David R. Sargan, Karen Miller, Karl G. LarkAbstract:Addison's disease, an immune-mediated disorder caused by destruction of the adrenal glands, is a rare disorder of Western European populations. Studies indicate that the disorder is polygenic in nature, involving specific alleles of the CTLA-4, DRB1*04 and DQ, Cyp27B1, VDR and MIC-A and -B loci. A similar immune form of Addison's disease occurs in several breeds of domestic Dog, with frequencies ranging from 1.5 to 9.0%. The high frequency of the disease in domestic Dog breeds likely reflects the small number of founders associated with many breeds, subsequent inbreeding, and the frequent use of popular sires. The Portuguese Water Dog (PWD) is a significantly affected breed. An analysis of 11,384 PWDs surveyed between 1985 and 1996 suggests a breed-specific disease incidence of 1.5%. As with humans, the disease is typically of late onset. This study involves a genetic comparison of Addison's disease in the PWD to the analogous disease in humans. The study is facilitated by the existence of complete pedigrees and a relatively high degree of inbreeding among PWDs. The breed originated from 31 founders, with 10 animals responsible for 90% of the current gene pool. We describe, specifically, the identification of two disease-associated loci, on Canis familiaris (CFA) chromosomes CFA12 and 37, which are syntenic with the human DRB1 histocompatibility locus alleles HLA-DRB1*04 and DRB1*0301, and to a locus for immunosuppression syntenic with CTLA-4. Strong similarities exist therefore in the complex genetic background of Addison's disease in humans and in the PWD. With the completion of the canine and human genome sequence, the Purebred Dog is set to become an important comparative model for Addison's as well as other human immune disorders.
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The domestic Dog genome.
Current biology : CB, 2004Co-Authors: Elaine A Ostrander, Kenine E. ComstockAbstract:Why are Dogs of interest to biologists? Over 400 breeds of Dog exist worldwide today, each a closed breeding population with a unique pattern of size, morphology and behavior. But the aggressive breeding programs used to create Purebred Dogs have burdened them with over 350 inherited disorders, many associated with just one or a few breeds. Breeds expanded rapidly from popular sires to meet breeders’ demands suffer the most. It has been suggested that the unique structure of the Purebred Dog population may greatly simplify the mapping of genes associated with complex traits that have proven intractable by studying human families.The canine genome map. The most recently published canine map, a joint venture between investigators at the University of Rennes and the Fred Hutchinson Cancer Research Center (FHCRC) has an average of one marker every 900 kb across the Dog's 38 autosomes and X and Y chromosomes. A minimal mapping set of 325 well distributed, highly polymorphic microsatellite markers is available for genome-wide scans of 8–10 cM density. Efforts are also underway, in collaboration with investigators at The Institute for Genomic Research (TIGR), to order 10,000 independent genes derived from the 1.5X sequence on the canine chromosomal map. This will provide a high density resource for comparative mapping between the human and Dog genome. The canine expressed sequence tag (EST) project, an additional resource, is providing a foundation for much needed canine expression arrays. The effort has been led by investigators at Cold Spring Harbor Laboratory who have already deposited over 10,000 random sequences constructed from brain, testes and MDCK cell cDNA libraries into a publicly available database (http://nucleus.cshl.edu/genseq/Dogweb/).The 1.5X canine genome sequence. Investigators at TIGR and the Center for Advancement of Genomics recently surveyed the Dog genome sequence and provided data summarizing 1.5X coverage from a Purebred male standard Poodle. The sequence is estimated to cover 77% of the genome and contains 6.22 million reads. More than 650 million base pairs of Dog sequence align uniquely to the human genome, and is estimated to include fragments for 18,473 of 24,567 annotated human genes. Estimates of the euchromatic genome size for Dog range from 2.31 to 2.47 billion base pairs, somewhat smaller than the human genome but similar to mouse. Comparison of human and Dog genomes by radiation hybrid mapping have revealed ∼85 conserved blocks. Analysis of the 1.5X sequence confirms most of these blocks, but predicts many additional syntenic breaks and suggests the final number of orthologous blocks is ∼200. Among the most interesting features of the canine genome is that ∼31% is composed of repetitive sequences, smaller than the 46% and 38% found in the human and mouse genomes, respectively. The most abundant repeat, a SINE element (SINEC_CF), is thought to be derived from tRNA sequences. An estimated 7% — 16,000 of 230,000 copies in the genome — of the SINEC_CF elements are bimorphic (two alleles) in the sequenced Poodle. By comparison, the number of bimorphic Alu sequences in humans is estimated to be only 1200.Mapping simple mendelian traits. Existing resources have been used to tackle the mapping of common canine disorders. The top 10 diseases in Purebred Dogs include several of major concern to human medicine, such as cancer, epilepsy, immunodeficiencies, retinal disease, cataracts and heart disease. Disease loci have been localized for several canine diseases; some highlight genes already suspected from studies of human disorders such as kidney cancer, hemophilia and immune disorders. Others, such as the hypocretin 2 receptor associated with narcolepsy in Doberman Pinschers, were previously unknown. The latter has opened new avenues of study regarding the biology of sleep.View Large Image | View Hi-Res Image | Download PowerPoint SlideThe 6X canine genome sequence and SNP mapping. Last year, a white paper submitted to support the 6X sequencing of the Dog genome received approval from NHGRI. Sequencing of a highly inbred female Boxer began at the Whitehead Genome Center in June 2003, with completion expected by Spring 2004. Plans are also underway to find single nucleotide polymorphisms (SNPs) in nine distinct breeds of Dog and a wolf. While final selection is still underway, breeds being selected represent significant phenotypic variation, distinct lineages and high levels of genomic variation.Mapping complex traits. The genome sequence has increased interest in using the Dog to map the genetics of complex traits. Most Dog breeds have been created in a few generations, so a small number of key loci are likely responsible for their characteristic features. A recent analysis of canid morphology in Portuguese Water Dogs demonstrates the value of breeds with limited numbers of founders for studies in quantitative genetics. Investigators at University of Utah identified four significant quantitative trait loci (QTLs) for distinct aspects of canine skeletal morphology. Similar approaches are now applied to the study of complex diseases such as hip dysplasia.Linkage disequilibrium mapping. The unique history of Dog breeds suggests that linkage disequilibrium (LD) mapping will be useful for identifying genes associated with both simple and complex traits. Additional studies will determine how truly polymorphic various Dog breeds are, how much haplotype information breeds with anecdotal histories share, and how far regions of LD extend across the Dog genome.Summary. The development of Dog breeds by selection for rarified traits represents one of the greatest experiments in biological variation ever done by man. The Dog genome map and DNA sequence offer great opportunities for understanding the genetic regulation that accounts for the greatest extremes of natural variation.
Heather J Huson - One of the best experts on this subject based on the ideXlab platform.
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A genetic dissection of breed composition and performance enhancement in the Alaskan sled Dog
BMC Genetics, 2010Co-Authors: Heather J Huson, Heidi G Parker, Jonathan Runstadler, Elaine A OstranderAbstract:Background The Alaskan sled Dog offers a rare opportunity to investigate the development of a Dog breed based solely on performance, rather than appearance, thus setting the breed apart from most others. Several established breeds, many of which are recognized by the American Kennel Club (AKC), have been introduced into the sled Dog population to enhance racing performance. We have used molecular methods to ascertain the constitutive breeds used to develop successful sled Dog lines, and in doing so, determined the breed origins of specific performance-related behaviors. One hundred and ninety-nine Alaskan sled Dogs were genotyped using 96 microsatellite markers that span the canine genome. These data were compared to that from 141 similarly genotyped Purebred Dog breeds. Sled Dogs were evaluated for breed composition based on a variety of performance phenotypes including speed, endurance and work ethic, and the data stratified based on population structure. Results We observe that the Alaskan sled Dog has a unique molecular signature and that the genetic profile is sufficient for identifying Dogs bred for sprint versus distance. When evaluating contributions of existing breeds we find that the Alaskan Malamute and Siberian Husky contributions are associated with enhanced endurance; Pointer and Saluki are associated with enhanced speed and the Anatolian Shepherd demonstrates a positive influence on work ethic. Conclusion We have established a genetic breed profile for the Alaskan sled Dog, identified profile variance between sprint and distance Dogs, and established breeds associated with enhanced performance attributes. These data set the stage for mapping studies aimed at finding genes that are associated with athletic attributes integral to the high performing Alaskan sled Dog.
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a genetic dissection of breed composition and performance enhancement in the alaskan sled Dog
BMC Genetics, 2010Co-Authors: Heidi G Parker, Jonathan Runstadler, Heather J Huson, Elaine A OstranderAbstract:The Alaskan sled Dog offers a rare opportunity to investigate the development of a Dog breed based solely on performance, rather than appearance, thus setting the breed apart from most others. Several established breeds, many of which are recognized by the American Kennel Club (AKC), have been introduced into the sled Dog population to enhance racing performance. We have used molecular methods to ascertain the constitutive breeds used to develop successful sled Dog lines, and in doing so, determined the breed origins of specific performance-related behaviors. One hundred and ninety-nine Alaskan sled Dogs were genotyped using 96 microsatellite markers that span the canine genome. These data were compared to that from 141 similarly genotyped Purebred Dog breeds. Sled Dogs were evaluated for breed composition based on a variety of performance phenotypes including speed, endurance and work ethic, and the data stratified based on population structure. We observe that the Alaskan sled Dog has a unique molecular signature and that the genetic profile is sufficient for identifying Dogs bred for sprint versus distance. When evaluating contributions of existing breeds we find that the Alaskan Malamute and Siberian Husky contributions are associated with enhanced endurance; Pointer and Saluki are associated with enhanced speed and the Anatolian Shepherd demonstrates a positive influence on work ethic. We have established a genetic breed profile for the Alaskan sled Dog, identified profile variance between sprint and distance Dogs, and established breeds associated with enhanced performance attributes. These data set the stage for mapping studies aimed at finding genes that are associated with athletic attributes integral to the high performing Alaskan sled Dog.
Cisca Wijmenga - One of the best experts on this subject based on the ideXlab platform.
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identification of a new copper metabolism gene by positional cloning in a Purebred Dog population
Human Molecular Genetics, 2002Co-Authors: Bart Van De Sluis, P L Pearson, Bernard A Van Oost, Jan Rothuizen, Cisca WijmengaAbstract:Domesticated animal species such as Dogs and cats, with their many different characteristics and breed-specific diseases, and their close relationship and shared environment with humans, are a potentially rich source for the identification of the genetic contribution to human biology and disease. Copper toxicosis in Bedlington terriers is a genetic disease occurring with a high prevalence worldwide and is unique to this breed. Copper homeostasis appears to be well regulated in mammals. Two copper carrier proteins have been identified in man and rodents which, when dysfunctional, cause either copper deficiency (Menkes disease) or copper accumulation in various tissues (Wilson disease). However, these proteins are not primarily involved in the biliary excretion of copper. Bedlington terriers have a high prevalence of copper toxicosis and it is well documented that their biliary excretion of copper is impaired. This disease is of direct relevance for the understanding of copper metabolism in mammals. Previously, we mapped the copper toxicosis gene to Dog chromosome region 10q26. Based on DNA samples obtained from privately owned Dogs, we were able to confine the localization of the copper toxicosis gene to a region of <500 kb by linkage disequilibrium mapping. While screening genes and expressed sequence tags in this region for mutations we found that exon 2 of the MURR1 gene is deleted in both alleles of all affected Bedlington terriers and in single alleles in obligate carriers. Although the function of the MURR1 gene is still unknown, the discovery of a mutated MURR1 gene in Bedlington terriers with copper toxicosis provides a new lead to disentangling the complexities of copper metabolism in mammals.
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Identification of a new copper metabolism gene by positional cloning in a Purebred Dog population.
Human Molecular Genetics, 2002Co-Authors: Bart Van De Sluis, P L Pearson, Bernard A Van Oost, Jan Rothuizen, Cisca WijmengaAbstract:Domesticated animal species such as Dogs and cats, with their many different characteristics and breed-specific diseases, and their close relationship and shared environment with humans, are a potentially rich source for the identification of the genetic contribution to human biology and disease. Copper toxicosis in Bedlington terriers is a genetic disease occurring with a high prevalence worldwide and is unique to this breed. Copper homeostasis appears to be well regulated in mammals. Two copper carrier proteins have been identified in man and rodents which, when dysfunctional, cause either copper deficiency (Menkes disease) or copper accumulation in various tissues (Wilson disease). However, these proteins are not primarily involved in the biliary excretion of copper. Bedlington terriers have a high prevalence of copper toxicosis and it is well documented that their biliary excretion of copper is impaired. This disease is of direct relevance for the understanding of copper metabolism in mammals. Previously, we mapped the copper toxicosis gene to Dog chromosome region 10q26. Based on DNA samples obtained from privately owned Dogs, we were able to confine the localization of the copper toxicosis gene to a region of
Heidi G Parker - One of the best experts on this subject based on the ideXlab platform.
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A genetic dissection of breed composition and performance enhancement in the Alaskan sled Dog
BMC Genetics, 2010Co-Authors: Heather J Huson, Heidi G Parker, Jonathan Runstadler, Elaine A OstranderAbstract:Background The Alaskan sled Dog offers a rare opportunity to investigate the development of a Dog breed based solely on performance, rather than appearance, thus setting the breed apart from most others. Several established breeds, many of which are recognized by the American Kennel Club (AKC), have been introduced into the sled Dog population to enhance racing performance. We have used molecular methods to ascertain the constitutive breeds used to develop successful sled Dog lines, and in doing so, determined the breed origins of specific performance-related behaviors. One hundred and ninety-nine Alaskan sled Dogs were genotyped using 96 microsatellite markers that span the canine genome. These data were compared to that from 141 similarly genotyped Purebred Dog breeds. Sled Dogs were evaluated for breed composition based on a variety of performance phenotypes including speed, endurance and work ethic, and the data stratified based on population structure. Results We observe that the Alaskan sled Dog has a unique molecular signature and that the genetic profile is sufficient for identifying Dogs bred for sprint versus distance. When evaluating contributions of existing breeds we find that the Alaskan Malamute and Siberian Husky contributions are associated with enhanced endurance; Pointer and Saluki are associated with enhanced speed and the Anatolian Shepherd demonstrates a positive influence on work ethic. Conclusion We have established a genetic breed profile for the Alaskan sled Dog, identified profile variance between sprint and distance Dogs, and established breeds associated with enhanced performance attributes. These data set the stage for mapping studies aimed at finding genes that are associated with athletic attributes integral to the high performing Alaskan sled Dog.
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a genetic dissection of breed composition and performance enhancement in the alaskan sled Dog
BMC Genetics, 2010Co-Authors: Heidi G Parker, Jonathan Runstadler, Heather J Huson, Elaine A OstranderAbstract:The Alaskan sled Dog offers a rare opportunity to investigate the development of a Dog breed based solely on performance, rather than appearance, thus setting the breed apart from most others. Several established breeds, many of which are recognized by the American Kennel Club (AKC), have been introduced into the sled Dog population to enhance racing performance. We have used molecular methods to ascertain the constitutive breeds used to develop successful sled Dog lines, and in doing so, determined the breed origins of specific performance-related behaviors. One hundred and ninety-nine Alaskan sled Dogs were genotyped using 96 microsatellite markers that span the canine genome. These data were compared to that from 141 similarly genotyped Purebred Dog breeds. Sled Dogs were evaluated for breed composition based on a variety of performance phenotypes including speed, endurance and work ethic, and the data stratified based on population structure. We observe that the Alaskan sled Dog has a unique molecular signature and that the genetic profile is sufficient for identifying Dogs bred for sprint versus distance. When evaluating contributions of existing breeds we find that the Alaskan Malamute and Siberian Husky contributions are associated with enhanced endurance; Pointer and Saluki are associated with enhanced speed and the Anatolian Shepherd demonstrates a positive influence on work ethic. We have established a genetic breed profile for the Alaskan sled Dog, identified profile variance between sprint and distance Dogs, and established breeds associated with enhanced performance attributes. These data set the stage for mapping studies aimed at finding genes that are associated with athletic attributes integral to the high performing Alaskan sled Dog.
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Human Genetics and the Canine System
Vogel and Motulsky's Human Genetics, 2010Co-Authors: Heidi G Parker, Elaine A OstranderAbstract:With constant advances in canine genomics, the Dog has found a permanent position as a source of genetic information for the inheritance of morphologic traits and disease susceptibility. The modern domestic Dog is not a typical model organism. They share our environment, our life-styles and often our food. In addition, they experience many of the same diseases that people do and are diagnosed and treated using the same medical procedures and pharmaceuticals. However, unlike humans, the Purebred Dog maintains a highly structured population organization that, if used correctly, can simplify the genetics of complex traits and disorders. In this chapter, we will discuss the history of canine genomics along with recent advances in resource development. Specific examples will be provided to demonstrate strategies for using population stratification to the best advantage in mapping traits both simple and complex. Together, these data highlight the utility of the canine system for mapping traits and finding mutations important in both human and companion animal science.
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A 1-Mb resolution radiation hybrid map of the canine genome.
Proceedings of the National Academy of Sciences of the United States of America, 2003Co-Authors: Richard Guyon, Heidi G Parker, Corinne Renier, Travis D. Lorentzen, Christophe Hitte, Lisa Kim, Edouard Cadieu, Pascale Quignon, Jennifer K. Lowe, Boris GelfenbeynAbstract:The Purebred Dog population consists of >300 partially inbred genetic isolates or breeds. Restriction of gene flow between breeds, together with strong selection for traits, has led to the establishment of a unique resource for dissecting the genetic basis of simple and complex mammalian traits. Toward this end, we present a comprehensive radiation hybrid map of the canine genome composed of 3,270 markers including 1,596 microsatellite-based markers, 900 cloned gene sequences and ESTs, 668 canine-specific bacterial artificial chromosome (BAC) ends, and 106 sequence-tagged sites. The map was constructed by using the RHDF5000-2 whole-genome radiation hybrid panel and computed by using multimap and tsp/concorde. The 3,270 markers map to 3,021 unique positions and define an average intermarker distance corresponding to 1 Mb. We also define a minimal screening set of 325 highly informative well spaced markers, to be used in the initiation of genome-wide scans. The well defined synteny between the Dog and human genomes, established in part as a function of this work by the identification of 85 conserved fragments, will allow follow-up of initial findings of linkage by selection of candidate genes from the human genome sequence. This work continues to define the canine system as the method of choice in the pursuit of the genes causing mammalian variation and disease.
