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Bioinformatics mining for disease causing mutations

using the dog genome as a model for human disease

Truvé, Katarina (2012). Bioinformatics mining for disease causing mutations. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis Agriculturae Sueciae, 1652-6880 ; 2012:64
ISBN 978-91-576-7711-2
[Doctoral thesis]

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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.

Authors/Creators:Truvé, Katarina
Title:Bioinformatics mining for disease causing mutations
Subtitle:using the dog genome as a model for human disease
Series Name/Journal:Acta Universitatis Agriculturae Sueciae
Year of publishing :2012
Number of Pages:67
I.Wilbe M, Jokinen P*, Truvé K*, Seppala EH, Karlsson EK, Biagi T, Hughes A, Bannasch D, Andersson G, Hansson-Hamlin H, Lohi H, Lindblad-Toh K. (2010) Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex. Nature Genetics. 42(3):250-254.
II.Olsson M, Meadows JR*, Truvé K*, Rosengren Pielberg G*, Puppo F*, Mauceli E, Quilez J, Tonomura N, Zanna G, Docampo MJ, Bassols A, Avery AC, Karlsson EK, Thomas A, Kastner DL, Bongcam-Rudloff E, Webster MT, Sanchez A, Hedhammar A, Remmers EF, Andersson L, Ferrer L, Tintle L, Lindblad-Toh K. (2011) A novel unstable duplication upstream of HAS2 predisposes to a breed-defining skin phenotype and a periodic fever syndrome in Chinese Shar-Pei dogs. PLoS Genetics. 7(3):e1001332.
III.Truvé K, Eriksson O, Norling M, Wilbe M, Mauceli E, Lindblad-Toh K, Bongcam-Rudloff E. (2011) SEQscoring: a tool to facilitate the interpretation of data generated with next generation sequencing technologies. EMBnet journal, 17.1 38-45.
IV.Truvé K, Dickinson P, York D, Rosengren Pielberg G, Perloski M, Murén E, Fuxelius HH, Andersson G, Hedhammar Å, Bongcam-Rudloff E, Lindblad-Toh K, Bannasch D. (2012) Identification of a glioma susceptibility locus in the wake of selective dog breeding for brachycephaly. Manuscript.
UNSPECIFIED*These authors contributed equally
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 (until Jan 2017)
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)
Permanent URL:
ID Code:9081
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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