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Mapping trait genes in dogs

using the dog as a model organism

Baranowska Körberg, Izabella (2011). Mapping trait genes in dogs. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis agriculturae Sueciae, 1652-6880 ; 2011:69
ISBN 978-91-576-7613-9
[Doctoral thesis]

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Abstract

Understanding the genetic background of a given phenotypic trait or disease has long intrigued scientists. Model organisms can be employed when it is not feasible or possible to find trait causality in human cohorts. This thesis reports the mapping of both a phenotypic trait (white spotting) and a disease (sensory ataxic neuropathy) in dogs, and in doing so highlights the potential of the dog as a model organism for mapping traits of relevance to human health and biology.

For white spotting, a two-stage mapping approach was used to identify an associated genomic region, which contained only the microphtalmia-associated transcription factor (MITF) gene. Stage 1: a genome-wide association analysis in a single breed, taking advantage of the extensive within breed linkage disequilibrium (LD) and long haplotypes, identified a discrete region of approximately 1 Mb. Stage 2: finemapping in an additional breed presenting the same phenotype, exploiting the short LD and haplotypes shared across dog breeds, was used to narrow the region to about 100 kb. We functionally evaluated two candidate polymorphisms associated with MITF, a SINE insertion and a length polymorphism upstream of the melanocyte-specific transcription start site of MITF. The data indicated that both polymorphisms affect transcription from the MITF-M promoter.

Sensory ataxic neuropathy (SAN) is a neurological disorder affecting a specific maternal lineage of Golden Retrievers. We identified a one base pair deletion in mitochondrial tRNATyr and through biochemical analyses of mitochondria and functional studies of the deletion, confirmed causality and the mitochondrial origin of SAN. This is one of the first mitochondrial disorders identified in dogs and we additionally developed a genetic test for the public to allow for the elimination of the disease from this breed.

The genetic and functional analyses of both white spotting coat colour and SAN in dogs, which are controlled by mutations of the two different genomes, clearly demonstrate the utility of the canine model and establish a new role for man's best friend.

Authors/Creators:Baranowska Körberg, Izabella
Title:Mapping trait genes in dogs
Subtitle:using the dog as a model organism
Series/Journal:Acta Universitatis agriculturae Sueciae (1652-6880)
Year of publishing :2011
Volume:2011:69
Number of Pages:66
Papers/manuscripts:
NumberReferences
I.Karlsson, E. K., Baranowska, I., Wade, C. M., Salmon Hillbertz, N.H. C., Zody, M. C., Anderson, N., Biagi, T. M., Patterson, N.,Rosengren Pielberg, G., Kulbokas III, E. J., Comstock, K. E., Keller, E.T., Mesirov, J. P., von Euler, H., Kämpe, O., Hedhammar, Å., Lander,E. S., Andersson, G., Andersson, L. & Lindblad-Toh, K. (2007). Efficient Mapping of Mendelian Traits in Dogs Through Genome-Wide Association. Nature Genetics 39(11), 1321-1328.
II.Baranowska, I., Hultin Jäderlund, K., Nennesmo, I., Holmqvist, E., Heidrich, N., Larsson, N.-G., Andersson, G., Wagner, E. G. H., Hedhammar, Å., Wibom, R. & Andersson, L. (2009). Sensory Ataxic Neuropathy in Golden Retriever Dogs Is Caused by a Deletion in the Mitochondrial tRNATyr Gene. PLoS Genetics 5(5), e1000499. doi:10.1371/journal.pgen.1000499
III.Baranowska Körberg, I., Zhang X., Rosengren Pielberg, G., Gustafson, U., Karlsson, E. K., Hedhammar, Å., Lindblad-Toh, K.,Andersson, G. & Andersson, L. Functional Studies of Sequence Polymorphisms at the MITF Locus Associated with White Spotting in Dogs. (manuscript). Papers I and II are reproduced with the permission of the publishers.
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:978-91-576-7613-9
ISSN:1652-6880
Language:English
Publication Type:Doctoral thesis
Full Text Status:Public
Agris subject categories.:L Animal production > L10 Animal genetics and breeding
Subjects:Obsolete subject words > NATURAL SCIENCES
Obsolete subject words > VETERINARY MEDICINE
(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 > 4 Agricultural Sciences > 404 Agricultural Biotechnology > Genetics and Breeding
Agrovoc terms:dogs, genes, genetic mapping, animal models, genetic inheritance
Keywords:dog, model organism, two-stage association mapping, mitochondrial disorder
URN:NBN:urn:nbn:se:slu:epsilon-e-207
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-207
ID Code:8320
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Animal Breeding and Genetics
Deposited By: Mrs Izabella Baranowska Körberg
Deposited On:12 Sep 2011 12:31
Metadata Last Modified:02 Dec 2014 10:47

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