using the dog genome as a model for human disease
Bioinformatics mining for disease causing mutations.
Acta Universitatis agriculturae Sueciae, 1652-6880
Humans and dogs share many common diseases, and it has been shown that the identification of mutations that cause disease in dogs can help unravel the genetic basis for a similar disease in humans. Mapping of traits and disease in dogs is not a new idea, but the sequencing of the whole dog genome, the creation of a dense SNP maps followed by the development of SNP arrays for high throughput genotyping has led to new facilitated mapping procedures. Each dog breed can be seen as a genetic isolate and certain breeds are often predisposed to specific diseases. Because of the genomic structure of the dog genome and the availability of new resources for disease mapping, the dog has been proposed to be especially advantageous for the mapping of complex disease that is difficult to map in human outbred populations.
In this thesis, the aim has been to identify disease-causing mutations for three complex diseases in dogs with the presence of similar conditions in humans. Emphasis has been on bioinformatics analyses of genome-wide SNP and large re-sequencing data.
In the dog breed Nova Scotia duck tolling retriever it is common with an immune-mediated disease complex that resembles human systemic lupus erythematosus (SLE). In paper I we used a two-stage genome-wide association mapping method and successfully located several susceptibility loci in dogs for this disease complex. In paper II we identified a mutation that had been under selection in the Shar-Pei breed, causing both a breed-defining wrinkled skin phenotype and an autoinflammatory fever disease. Because the locus had been under selection we used an alternative mapping approach, called homozygosity mapping to identify the locus, followed by re-sequencing using next generation sequencing technologies. In paper III we report the development of a web-based tool that facilitates analyses and extraction of essential information from the large amount of data produced by next generation sequencing projects. In paper IV we used across-breed genome-wide association mapping to identify risk factors for glioma, a type of malignant brain tumor fatal to both human and dogs. For the three diseases excellent candidate genes have been identified, and continued research might has the potential to lead to better treatment options and thus benefit both dogs and humans.
|Title:||Bioinformatics mining for disease causing mutations|
|Subtitle:||using the dog genome as a model for human disease|
|Series/Journal:||Acta Universitatis agriculturae Sueciae (1652-6880)|
|Year of publishing :||2012|
|Number of Pages:||67|
|Place of Publication:||Uppsala|
|Publisher:||Dept. of Animal Breeding and Genetics, Swedish University of Agricultural Sciences|
|Associated Programs and Other Stakeholders:||SLU - Research Areas for the Future > Future Animal Health and Welfare|
|ISBN for printed version:||978-91-576-7711-2|
|Publication Type:||Doctoral thesis|
|Full Text Status:||Public|
|Agris subject categories.:||L Animal production > L10 Animal genetics and breeding|
L Animal production > L73 Animal diseases
|Subjects:||(A) Swedish standard research categories 2011 > 1 Natural sciences > 102 Computer and Information Science > 10203 Bioinformatics (Computational Biology) (applications to be 10610)|
(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Genetics (medical genetics to be 30107 and agricultural genetics to be 40402)
(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Bioinformatics and Systems Biology (methods development to be 10203)
(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Medical Genetics
|Agrovoc terms:||dogs, breeds (animals), bioinformatics, animal diseases, lupus erythematosus, neoplasms, mutation, genomes, genetic maps, animal models|
|Keywords:||dog, genome-wide association mapping, homozygosity mapping, next generation sequencing, glioma, autoinflammatory disease, systemic lupus erythematosus (SLE)|
|Faculty:||VH - Faculty of Veterinary Medicine and Animal Science|
|Department:||(VH) > Dept. of Animal Breeding and Genetics|
|Deposited By:||Katarina Truvé|
|Deposited On:||21 Sep 2012 12:42|
|Metadata Last Modified:||02 Dec 2014 10:52|
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