Breed Relationships Facilitate Fine-Mapping Studies: A 7.8-kb Deletion Cosegregates With Collie Eye Anomaly Across Multiple Dog Breeds

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dc.contributor.authorAguirre, Gustavo D
dc.contributor.authorAguirre, Gustavo D
dc.contributor.authorKukekova, Anna V
dc.contributor.authorAkey, Danya T
dc.contributor.authorGoldstein, Orly
dc.contributor.authorKirkness, Ewen F
dc.contributor.authorBaysac, Kathleen C
dc.contributor.authorMosher, Dana S
dc.contributor.authorAcland, Gregory M
dc.contributor.authorOstrander, Elaine A
dc.date2023-05-17T09:46:43.000
dc.date.accessioned2023-05-23T04:45:50Z
dc.date.available2023-05-23T04:45:50Z
dc.date.issued2007-10-01
dc.date.submitted2014-10-17T06:58:51-07:00
dc.description.abstractThe features of modern dog breeds that increase the ease of mapping common diseases, such as reduced heterogeneity and extensive linkage disequilibrium, may also increase the difficulty associated with fine mapping and identifying causative mutations. One way to address this problem is by combining data from multiple breeds segregating the same trait after initial linkage has been determined. The multibreed approach increases the number of potentially informative recombination events and reduces the size of the critical haplotype by taking advantage of shortened linkage disequilibrium distances found across breeds. In order to identify breeds that likely share a trait inherited from the same ancestral source, we have used cluster analysis to divide 132 breeds of dog into five primary breed groups. We then use the multibreed approach to fine-map Collie eye anomaly (cea), a complex disorder of ocular development that was initially mapped to a 3.9-cM region on canine chromosome 37. Combined genotypes from affected individuals from four breeds of a single breed group significantly narrowed the candidate gene region to a 103-kb interval spanning only four genes. Sequence analysis revealed that all affected dogs share a homozygous deletion of 7.8 kb in the NHEJ1 gene. This intronic deletion spans a highly conserved binding domain to which several developmentally important proteins bind. This work both establishes that the primary cea mutation arose as a single disease allele in a common ancestor of herding breeds as well as highlights the value of comparative population analysis for refining regions of linkage.
dc.identifier.urihttps://repository.upenn.edu/handle/20.500.14332/49002
dc.legacy.articleid1071
dc.legacy.fields10.1101/gr.6772807
dc.legacy.fulltexturlhttps://repository.upenn.edu/cgi/viewcontent.cgi?article=1071&context=vet_papers&unstamped=1
dc.rights<p>This article is available under a Creative Commons License <a href="http://creativecommons.org/licenses/by-nc/3.0/">(Attribution-NonCommercial 3.0 Unported License)</a>.</p>
dc.source.beginpage1562
dc.source.endpage1571
dc.source.issue81
dc.source.issue11
dc.source.journalDepartmental Papers (Vet)
dc.source.journaltitleGenome Research
dc.source.peerreviewedtrue
dc.source.statuspublished
dc.source.volume17
dc.subject.othermodern dog breeds
dc.subject.othermultibreed approach
dc.subject.otherCollie eye anomaly
dc.subject.otherMedicine and Health Sciences
dc.subject.otherVeterinary Medicine
dc.titleBreed Relationships Facilitate Fine-Mapping Studies: A 7.8-kb Deletion Cosegregates With Collie Eye Anomaly Across Multiple Dog Breeds
dc.typeArticle
digcom.contributor.authorParker, Heidi G
digcom.contributor.authorKukekova, Anna V
digcom.contributor.authorAkey, Danya T
digcom.contributor.authorGoldstein, Orly
digcom.contributor.authorKirkness, Ewen F
digcom.contributor.authorBaysac, Kathleen C
digcom.contributor.authorMosher, Dana S
digcom.contributor.authorisAuthorOfPublication|email:gda@vet.upenn.edu|institution:University of Pennsylvania|Aguirre, Gustavo D
digcom.contributor.authorAcland, Gregory M
digcom.contributor.authorOstrander, Elaine A
digcom.identifiervet_papers/81
digcom.identifier.contextkey6246871
digcom.identifier.submissionpathvet_papers/81
digcom.typearticle
dspace.entity.typePublication
person.identifier.orcid0000-0002-5228-256X
person.identifier.orcid0000-0002-5228-256X
relation.isAuthorOfPublication1a18ef39-6294-4816-a00d-fe4b64c3295a
relation.isAuthorOfPublication1a18ef39-6294-4816-a00d-fe4b64c3295a
relation.isAuthorOfPublication.latestForDiscovery1a18ef39-6294-4816-a00d-fe4b64c3295a
upenn.schoolDepartmentCenterDepartmental Papers (Vet)
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