Evaluation of the major histocompatibility complex (MHC) class II as a candidate for sudden acquired retinal degeneration syndrome (SARDS) in Dachshunds

Stephanie J. Stromberg, Sara M. Thomasy, Ariana D. Marangakis, Soohyun Kim, Ann E. Cooper, Emily A. Brown, David J. Maggs, Danika L. Bannasch

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Objective: Sudden acquired retinal degeneration syndrome (SARDS) is one of the leading causes of acute blindness in dogs, with an unknown etiology and no effective treatment. Certain breeds such as Dachshunds are overrepresented among SARDS patients, and therefore, the syndrome is suspected to have a genetic component. The objective of this study was to determine if a genetic locus associated with SARDS in Dachshunds could be identified using a genome-wide association study (GWAS). Procedures: Genome-wide association mapping was performed in 15 SARDS-affected and 16 unaffected Dachshunds. Genotyping of three classical DLA class II genes (DLA-DRB1, DLA-DQA1, and DLA-DQB1) was performed in 34 SARDS-affected and 66 unaffected Dachshunds to evaluate for an association in this region. Results: Although no single nucleotide polymorphisms (SNPs) were of genome-wide statistical significance (PBonferroni < 0.05), 5 of the top 9 SNPs were in the major histocompatibility complex (MHC). Using DLA typing, the allele DLA-DRB1*09401 was identified as a risk factor for the development of SARDS (P = 0.0032, OR = 4.0). The alleles DLA-DQB1*00101 (P = 0.0050, OR = 0.31), DLA-DQA1*00901 (P = 0.0087, OR = 0.33), and a previously identified DLA-DRB1allele described as “DRB1-T” (P = 0.0284, OR = 0.37) were identified as protective factors. Conclusions: Although far from definitive, association of SARDS with alleles of immunologic importance further supports the hypothesis that autoimmunity may play a role in the pathogenesis of SARDS.

Original languageEnglish (US)
Pages (from-to)751-759
Number of pages9
JournalVeterinary Ophthalmology
Volume22
Issue number6
DOIs
StatePublished - Nov 1 2019

Fingerprint

Dachshund
Retinal Degeneration
major histocompatibility complex
Major Histocompatibility Complex
alleles
single nucleotide polymorphism
autoimmunity
genome
blindness
Alleles
genotyping
chromosome mapping
etiology
Single Nucleotide Polymorphism
risk factors
pathogenesis
breeds
Genome
loci
dogs

Keywords

  • Dachshund
  • DLA
  • dog leukocyte antigen
  • genome-wide association studies
  • MHC
  • sudden acquired retinal degeneration syndrome

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Evaluation of the major histocompatibility complex (MHC) class II as a candidate for sudden acquired retinal degeneration syndrome (SARDS) in Dachshunds. / Stromberg, Stephanie J.; Thomasy, Sara M.; Marangakis, Ariana D.; Kim, Soohyun; Cooper, Ann E.; Brown, Emily A.; Maggs, David J.; Bannasch, Danika L.

In: Veterinary Ophthalmology, Vol. 22, No. 6, 01.11.2019, p. 751-759.

Research output: Contribution to journalArticle

@article{923192d359fb47f89b3d465bec025f1e,
title = "Evaluation of the major histocompatibility complex (MHC) class II as a candidate for sudden acquired retinal degeneration syndrome (SARDS) in Dachshunds",
abstract = "Objective: Sudden acquired retinal degeneration syndrome (SARDS) is one of the leading causes of acute blindness in dogs, with an unknown etiology and no effective treatment. Certain breeds such as Dachshunds are overrepresented among SARDS patients, and therefore, the syndrome is suspected to have a genetic component. The objective of this study was to determine if a genetic locus associated with SARDS in Dachshunds could be identified using a genome-wide association study (GWAS). Procedures: Genome-wide association mapping was performed in 15 SARDS-affected and 16 unaffected Dachshunds. Genotyping of three classical DLA class II genes (DLA-DRB1, DLA-DQA1, and DLA-DQB1) was performed in 34 SARDS-affected and 66 unaffected Dachshunds to evaluate for an association in this region. Results: Although no single nucleotide polymorphisms (SNPs) were of genome-wide statistical significance (PBonferroni < 0.05), 5 of the top 9 SNPs were in the major histocompatibility complex (MHC). Using DLA typing, the allele DLA-DRB1*09401 was identified as a risk factor for the development of SARDS (P = 0.0032, OR = 4.0). The alleles DLA-DQB1*00101 (P = 0.0050, OR = 0.31), DLA-DQA1*00901 (P = 0.0087, OR = 0.33), and a previously identified DLA-DRB1allele described as “DRB1-T” (P = 0.0284, OR = 0.37) were identified as protective factors. Conclusions: Although far from definitive, association of SARDS with alleles of immunologic importance further supports the hypothesis that autoimmunity may play a role in the pathogenesis of SARDS.",
keywords = "Dachshund, DLA, dog leukocyte antigen, genome-wide association studies, MHC, sudden acquired retinal degeneration syndrome",
author = "Stromberg, {Stephanie J.} and Thomasy, {Sara M.} and Marangakis, {Ariana D.} and Soohyun Kim and Cooper, {Ann E.} and Brown, {Emily A.} and Maggs, {David J.} and Bannasch, {Danika L.}",
year = "2019",
month = "11",
day = "1",
doi = "10.1111/vop.12646",
language = "English (US)",
volume = "22",
pages = "751--759",
journal = "Veterinary Ophthalmology",
issn = "1463-5216",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - Evaluation of the major histocompatibility complex (MHC) class II as a candidate for sudden acquired retinal degeneration syndrome (SARDS) in Dachshunds

AU - Stromberg, Stephanie J.

AU - Thomasy, Sara M.

AU - Marangakis, Ariana D.

AU - Kim, Soohyun

AU - Cooper, Ann E.

AU - Brown, Emily A.

AU - Maggs, David J.

AU - Bannasch, Danika L.

PY - 2019/11/1

Y1 - 2019/11/1

N2 - Objective: Sudden acquired retinal degeneration syndrome (SARDS) is one of the leading causes of acute blindness in dogs, with an unknown etiology and no effective treatment. Certain breeds such as Dachshunds are overrepresented among SARDS patients, and therefore, the syndrome is suspected to have a genetic component. The objective of this study was to determine if a genetic locus associated with SARDS in Dachshunds could be identified using a genome-wide association study (GWAS). Procedures: Genome-wide association mapping was performed in 15 SARDS-affected and 16 unaffected Dachshunds. Genotyping of three classical DLA class II genes (DLA-DRB1, DLA-DQA1, and DLA-DQB1) was performed in 34 SARDS-affected and 66 unaffected Dachshunds to evaluate for an association in this region. Results: Although no single nucleotide polymorphisms (SNPs) were of genome-wide statistical significance (PBonferroni < 0.05), 5 of the top 9 SNPs were in the major histocompatibility complex (MHC). Using DLA typing, the allele DLA-DRB1*09401 was identified as a risk factor for the development of SARDS (P = 0.0032, OR = 4.0). The alleles DLA-DQB1*00101 (P = 0.0050, OR = 0.31), DLA-DQA1*00901 (P = 0.0087, OR = 0.33), and a previously identified DLA-DRB1allele described as “DRB1-T” (P = 0.0284, OR = 0.37) were identified as protective factors. Conclusions: Although far from definitive, association of SARDS with alleles of immunologic importance further supports the hypothesis that autoimmunity may play a role in the pathogenesis of SARDS.

AB - Objective: Sudden acquired retinal degeneration syndrome (SARDS) is one of the leading causes of acute blindness in dogs, with an unknown etiology and no effective treatment. Certain breeds such as Dachshunds are overrepresented among SARDS patients, and therefore, the syndrome is suspected to have a genetic component. The objective of this study was to determine if a genetic locus associated with SARDS in Dachshunds could be identified using a genome-wide association study (GWAS). Procedures: Genome-wide association mapping was performed in 15 SARDS-affected and 16 unaffected Dachshunds. Genotyping of three classical DLA class II genes (DLA-DRB1, DLA-DQA1, and DLA-DQB1) was performed in 34 SARDS-affected and 66 unaffected Dachshunds to evaluate for an association in this region. Results: Although no single nucleotide polymorphisms (SNPs) were of genome-wide statistical significance (PBonferroni < 0.05), 5 of the top 9 SNPs were in the major histocompatibility complex (MHC). Using DLA typing, the allele DLA-DRB1*09401 was identified as a risk factor for the development of SARDS (P = 0.0032, OR = 4.0). The alleles DLA-DQB1*00101 (P = 0.0050, OR = 0.31), DLA-DQA1*00901 (P = 0.0087, OR = 0.33), and a previously identified DLA-DRB1allele described as “DRB1-T” (P = 0.0284, OR = 0.37) were identified as protective factors. Conclusions: Although far from definitive, association of SARDS with alleles of immunologic importance further supports the hypothesis that autoimmunity may play a role in the pathogenesis of SARDS.

KW - Dachshund

KW - DLA

KW - dog leukocyte antigen

KW - genome-wide association studies

KW - MHC

KW - sudden acquired retinal degeneration syndrome

UR - http://www.scopus.com/inward/record.url?scp=85073708142&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85073708142&partnerID=8YFLogxK

U2 - 10.1111/vop.12646

DO - 10.1111/vop.12646

M3 - Article

C2 - 30791205

AN - SCOPUS:85073708142

VL - 22

SP - 751

EP - 759

JO - Veterinary Ophthalmology

JF - Veterinary Ophthalmology

SN - 1463-5216

IS - 6

ER -