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Identification of genomic regions associated with phenotypic variation between dog breeds using selection mapping
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2011 (English)In: PLoS Genetics, ISSN 1553-7404, Vol. 7, no 10, e1002316- p.Article in journal (Refereed) Published
Abstract [en]

The extraordinary phenotypic diversity of dog breeds has been sculpted by a unique population history accompanied by selection for novel and desirable traits. Here we perform a comprehensive analysis using multiple test statistics to identify regions under selection in 509 dogs from 46 diverse breeds using a newly developed high-density genotyping array consisting of >170,000 evenly spaced SNPs. We first identify 44 genomic regions exhibiting extreme differentiation across multiple breeds. Genetic variation in these regions correlates with variation in several phenotypic traits that vary between breeds, and we identify novel associations with both morphological and behavioral traits. We next scan the genome for signatures of selective sweeps in single breeds, characterized by long regions of reduced heterozygosity and fixation of extended haplotypes. These scans identify hundreds of regions, including 22 blocks of homozygosity longer than one megabase in certain breeds. Candidate selection loci are strongly enriched for developmental genes. We chose one highly differentiated region, associated with body size and ear morphology, and characterized it using high-throughput sequencing to provide a list of variants that may directly affect these traits. This study provides a catalogue of genomic regions showing extreme reduction in genetic variation or population differentiation in dogs, including many linked to phenotypic variation. The many blocks of reduced haplotype diversity observed across the genome in dog breeds are the result of both selection and genetic drift, but extended blocks of homozygosity on a megabase scale appear to be best explained by selection. Further elucidation of the variants under selection will help to uncover the genetic basis of complex traits and disease.

Place, publisher, year, edition, pages
2011. Vol. 7, no 10, e1002316- p.
National Category
Natural Sciences
URN: urn:nbn:se:uu:diva-162827DOI: 10.1371/journal.pgen.1002316ISI: 000296665400017PubMedID: 22022279OAI: oai:DiVA.org:uu-162827DiVA: diva2:461765
Available from: 2011-12-05 Created: 2011-12-05 Last updated: 2014-09-19Bibliographically approved
In thesis
1. Detecting Signatures of Selection within the Dog Genome
Open this publication in new window or tab >>Detecting Signatures of Selection within the Dog Genome
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Deciphering the genetic basis of phenotypic diversity is one of the central aims of biological research. Domestic animals provide a unique opportunity for making substantial progress towards this goal. Intense positive selection has lead to a rich reservoir of phenotypes and underlying genotypes that can be interrogated using genetic tools to gain insight into the genetic basis of phenotypic diversity.

The dog is the most phenotypically diverse mammal. It was domesticated from the grey wolf 11-30,000 years ago. After domestication, a period of intense breeding has lead to the massive phenotypic diversity seen amongst dog breeds today. These two phases of strong positive selection at domestication and at breed creation are likely to have left their signature on the genome. In this thesis, we have analysed genome-wide patterns to detect genomic regions involved in selection in both of these phases. We used whole genome sequences from 60 dogs and 12 wolves, to detect dog domestication selective sweeps. We find evidence for genes involved in memory formation, neurotransmission and starch digestion.

To decipher the genetic signals underlying breed diversity, we used genome-wide genotype data from >170,000 SNPs in 509 dogs from 46 different breeds. We find evidence for genes under selection in many breeds, and only a few breeds. In addition, we identify novel sweeps underlying morphology and behavior.

Recombination can influence the configuration of alleles present on a haplotype, and can thus increase or decrease the efficiency of selection. The PRDM9 protein has been shown to be important for determining recombination hotspot locations in humans and other mammals, but of all the mammals studied so far the dog is the only one to have a non-functional PRDM9.

We used the genome-wide genotype data described above to characterise the fine scale recombination map in dogs. We find that recombination hotspots exist in dogs despite the absence of PRDM9. Moreover, we show that these hotspots are enriched for GC rich peaks and that these peaks are getting stronger over time. Our results show that the absence of PRDM9 has lead to the stabilisation of the recombination landscape in dogs.


Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 38 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 938
dog, evolution, domestication, PRDM9, recombination, positive selection, selective sweep
National Category
Evolutionary Biology Bioinformatics and Systems Biology Genetics
urn:nbn:se:uu:diva-209335 (URN)978-91-554-8783-6 (ISBN)
Public defence
2013-12-04, B42, BMC, Husargatan 3, Uppsala, 09:00 (English)
Available from: 2013-11-13 Created: 2013-10-17 Last updated: 2014-01-23

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Ratnakumar, AbhiramiAxelsson, ErikRosengren Pielberg, GerliLindblad-Toh, KerstinWebster, Matthew T
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