DNA testing and domestic dogs Mellersh, Cathryn
Mammalian genome,
02/2012, Letnik:
23, Številka:
1-2
Journal Article
Recenzirano
Odprti dostop
There are currently about 80 different DNA tests available for mutations that are associated with inherited disease in the domestic dog, and as the tools available with which to dissect the canine ...genome become increasingly sophisticated, this number can be expected to rise dramatically over the next few years. With unrelenting media pressure focused firmly on the health of the purebred domestic dog, veterinarians and dog breeders are turning increasingly to DNA tests to ensure the health of their dogs. It is ultimately the responsibility of the scientists who identify disease-associated genetic variants to make sensible choices about which discoveries are appropriate to develop into commercially available DNA tests for the lay dog breeder, who needs to balance the need to improve the genetic health of their breed with the need to maintain genetic diversity. This review discusses some of the factors that should be considered along the route from mutation discovery to DNA test and some representative examples of DNA tests currently available.
Canine inherited neurologic diseases are clinically varied and can be congenital, neonatal, or late onset as well as progressive or stationary. Modern genetic technologies are revolutionizing the ...speed and efficiency with which mutations responsible for inherited neurologic disease are being identified. Clinically similar disorders can be caused by different mutations, even within a single breed, and are thus genetically distinct. DNA tests can be used by dog breeders to reduce the prevalence of inherited neurologic disorders in specific breeds and help the veterinarian diagnose disease.
Mammalian species exhibit a wide range of lifespans. To date, a robust and dynamic molecular readout of these lifespan differences has not yet been identified. Recent studies have established the ...existence of ageing-associated differentially methylated positions (aDMPs) in human and mouse. These are CpG sites at which DNA methylation dynamics show significant correlations with age. We hypothesise that aDMPs are pan-mammalian and are a dynamic molecular readout of lifespan variation among different mammalian species.
A large-scale integrated analysis of aDMPs in six different mammals reveals a strong negative relationship between rate of change of methylation levels at aDMPs and lifespan. This relationship also holds when comparing two different dog breeds with known differences in lifespans. In an ageing cohort of aneuploid mice carrying a complete copy of human chromosome 21, aDMPs accumulate far more rapidly than is seen in human tissues, revealing that DNA methylation at aDMP sites is largely shaped by the nuclear trans-environment and represents a robust molecular readout of the ageing cellular milieu.
Overall, we define the first dynamic molecular readout of lifespan differences among mammalian species and propose that aDMPs will be an invaluable molecular tool for future evolutionary and mechanistic studies aimed at understanding the biological factors that determine lifespan in mammals.
Background
Hereditary sensory and autonomic neuropathies (HSANs) are a group of genetic disorders affecting the peripheral nervous system. Two different associated variants have been identified in ...dogs: 1 in Border Collies and 1 in Spaniels and Pointers.
Objectives
Clinically and genetically characterize HSAN in a family of mixed breed dogs.
Animals
Five 7‐month‐old mixed breed dogs from 2 related litters were presented for evaluation of a 2‐month history of acral mutilation and progressive pelvic limb gait abnormalities.
Methods
Complete physical, neurological, electrodiagnostic, and histopathological evaluations were performed. Whole genome sequencing of 2 affected dogs (1 from each litter) was used to identify variants that were homozygous or heterozygous in both cases, but wild type in 217 control genomes of 100 breeds. Immunohistochemistry was used to assess protein expression.
Results
Complete physical, neurological, electrodiagnostic, and histopathological evaluations confirmed a disorder affecting sensory and autonomic nerves. Whole genome sequencing identified a missense variant in the RETREG1 (reticulophagy regulator 1) gene (c.656C > T, p.P219L). All affected dogs were homozygous for the variant, which was not detected in 1193 dogs from different breeds. Immunohistochemistry showed no expression of RETREG1 in the cerebellum of affected dogs. One of the affected dogs lived for 5 years and showed gradual progression of the clinical signs.
Conclusions and Clinical Importance
We confirmed the diagnosis of HSAN in a family of mixed breed dogs and identified a novel and possibly pathogenic RETREG1 variant. Affected dogs experienced gradual deterioration over several years.
In 2003, the US National Human Genome Research Institute (NHGRI) agreed to fund a project to sequence the entire genome of a boxer dog named Tasha. Although the USA is a country of dog lovers, with ...approximately 38 million households owning one or more dogs, why did one of the National Institutes of Health countenance the use of 30 m dollars for such a purpose? The answer is that the NHGRI recognised the value of the dog as an unrivalled model for the study of human disease. In this paper, the reasons why the dog is such a good model are examined. Examples of where the study of disease in dogs is increasing the understanding of the genetic basis of human disease, of the development of improved diagnostic assays and of the evaluation of clinical therapies are provided.
Congenital deafness in the domestic dog is usually related to the presence of white pigmentation, which is controlled primarily by the piebald locus on chromosome 20 and also by merle on chromosome ...10. Pigment-associated deafness is also seen in other species, including cats, mice, sheep, alpacas, horses, cows, pigs, and humans, but the genetic factors determining why some piebald or merle dogs develop deafness while others do not have yet to be determined. Here we perform a genome-wide association study (GWAS) to identify regions of the canine genome significantly associated with deafness in three dog breeds carrying piebald: Dalmatian, Australian cattle dog, and English setter. We include bilaterally deaf, unilaterally deaf, and matched control dogs from the same litter, phenotyped using the brainstem auditory evoked response (BAER) hearing test. Principal component analysis showed that we have different distributions of cases and controls in genetically distinct Dalmatian populations, therefore GWAS was performed separately for North American and UK samples. We identified one genome-wide significant association and 14 suggestive (chromosome-wide) associations using the GWAS design of bilaterally deaf vs. control Australian cattle dogs. However, these associations were not located on the same chromosome as the piebald locus, indicating the complexity of the genetics underlying this disease in the domestic dog. Because of this apparent complex genetic architecture, larger sample sizes may be needed to detect the genetic loci modulating risk in piebald dogs.
Give a dog a genome Mellersh, Cathryn
The veterinary journal (1997),
10/2008, Letnik:
178, Številka:
1
Journal Article
Recenzirano
In 2004 the dog became only the fifth mammal to have its entire genome fully sequenced. The canine genome was sequenced in the hope that it would help scientists understand the complex evolutionary ...mechanisms that shape genes and genomes and provide a powerful tool for identifying genetic factors that contribute to human health and disease. It is expected that over the coming years the genome of man’s best friend will help in the understanding of the genetic cause of many inherited diseases that humans and dogs have in common. Not only of obvious benefit to humans, these studies will enable the development of DNA diagnostic tests that breeders can use to identify which of their dogs carry mutations that put them at risk of developing particular conditions and thus, over time, eliminate those diseases from the breed.