Home About Browse Search
Svenska


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

Bianchi, Matteo and Rafati, Nima and Karlsson, Asa and Muren, Eva and Rubin, Carl-Johan and Sundberg, Katarina and Andersson, Göran and Kampe, Olle and Hedhammar, Åke and Lindblad-Toh, Kerstin and Rosengren Pielberg, Gerli (2020). Whole-genome genotyping and resequencing reveal the association of a deletion in the complex interferon alpha gene cluster with hypothyroidism in dogs. BMC Genomics. 21 , 307 , 1-16
[Journal article]

[img] PDF - Published Version
Available under License Creative Commons Attribution.

2MB

Abstract

Background: Hypothyroidism 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.
Results: By 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.
Conclusions: Our 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.

Authors/Creators:Bianchi, Matteo and Rafati, Nima and Karlsson, Asa and Muren, Eva and Rubin, Carl-Johan and Sundberg, Katarina and Andersson, Göran and Kampe, Olle and Hedhammar, Åke and Lindblad-Toh, Kerstin and Rosengren Pielberg, Gerli
Title:Whole-genome genotyping and resequencing reveal the association of a deletion in the complex interferon alpha gene cluster with hypothyroidism in dogs
Year of publishing :2020
Volume:21
Article number:307
Number of Pages:16
Publisher:BMC
ISSN:1471-2164
Language:English
Publication Type:Journal article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(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 > 403 Veterinary Science > Clinical Science
Keywords:Dog, Hypothyroidism, Genome-wide association study, Fine-mapping, Whole-genome sequencing, Long-read sequencing, Type I interferon genes
URN:NBN:urn:nbn:se:slu:epsilon-p-105644
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-105644
Additional ID:
Type of IDID
DOI10.1186/s12864-020-6700-3
Web of Science (WoS)000528624600004
ID Code:17092
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Clinical Sciences
(VH) > Dept. of Animal Breeding and Genetics
Deposited By: SLUpub Connector
Deposited On:09 Jun 2020 06:37
Metadata Last Modified:09 Jun 2020 06:37

Repository Staff Only: item control page

Downloads

Downloads per year (since September 2012)

View more statistics

Downloads
Hits