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Research article - Peer-reviewed, 2020

Whole-genome genotyping and resequencing reveal the association of a deletion in the complex interferon alpha gene cluster with hypothyroidism in dogs

Bianchi, Matteo; Rafati, Nima; Karlsson, Asa; Muren, Eva; Rubin, Carl-Johan; Sundberg, Katarina; Andersson, Goran; Kampe, Olle; Hedhammar, Ake; Lindblad-Toh, Kerstin; Rosengren Pielberg, Gerli


BackgroundHypothyroidism is a common complex endocrinopathy that typically has an autoimmune etiology, and it affects both humans and dogs. Genetic and environmental factors are both known to play important roles in the disease development. In this study, we sought to identify the genetic risk factors potentially involved in the susceptibility to the disease in the high-risk Giant Schnauzer dog breed.ResultsBy employing genome-wide association followed by fine-mapping (top variant p-value=5.7x10(-6)), integrated with whole-genome resequencing and copy number variation analysis, we detected a similar to 8.9 kbp deletion strongly associated (p-value=0.0001) with protection against development of hypothyroidism. The deletion is located between two predicted Interferon alpha (IFNA) genes and it may eliminate functional elements potentially involved in the transcriptional regulation of these genes. Remarkably, type I IFNs have been extensively associated to human autoimmune hypothyroidism and general autoimmunity. Nonetheless, the extreme genomic complexity of the associated region on CFA11 warrants further long-read sequencing and annotation efforts in order to ascribe functions to the identified deletion and to characterize the canine IFNA gene cluster in more detail.ConclusionsOur results expand the current knowledge on genetic determinants of canine hypothyroidism by revealing a significant link with the human counterpart disease, potentially translating into better diagnostic tools across species, and may contribute to improved canine breeding strategies.


Dog; Hypothyroidism; Genome-wide association study; Fine-mapping; Whole-genome sequencing; Long-read sequencing; Type I interferon genes

Published in

BMC Genomics
2020, volume: 21, number: 1, article number: 307
Publisher: BMC

Authors' information

Bianchi, Matteo
Uppsala Univ
Rafati, Nima
Uppsala Univ
Karlsson, Asa
Uppsala Univ
Muren, Eva
Uppsala Univ
Rubin, Carl-Johan
Uppsala Univ
Sundberg, Katarina
Swedish University of Agricultural Sciences, Department of Animal Breeding and Genetics
Swedish University of Agricultural Sciences, Department of Animal Breeding and Genetics
Kampe, Olle
Karolinska Inst
Swedish University of Agricultural Sciences, Department of Clinical Sciences
Lindblad-Toh, Kerstin
Broad Inst MIT and Harvard
Rosengren Pielberg, Gerli
Uppsala Univ

UKÄ Subject classification

Clinical Science

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