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Doctoral thesis, 2012

Bioinformatics mining for disease causing mutations

Truvé, Katarina


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.


dog; genome-wide association mapping; homozygosity mapping; next generation sequencing; glioma; autoinflammatory disease; systemic lupus erythematosus (SLE)

Published in

Acta Universitatis Agriculturae Sueciae
2012, number: 2012:64
ISBN: 978-91-576-7711-2
Publisher: Dept. of Animal Breeding and Genetics, Swedish University of Agricultural Sciences

Authors' information

Truvé, Katarina
Swedish University of Agricultural Sciences, Department of Animal Breeding and Genetics

Associated SLU-program

Future Animal Health and Welfare (until Jan 2017)

UKÄ Subject classification

Bioinformatics (Computational Biology)
Bioinformatics and Systems Biology
Medical Genetics

URI (permanent link to this page)