Details

Autor(en) / Beteiligte

• Olsson, Mia
• Tintle, Linda
• Kierczak, Marcin
• Perloski, Michele
• Tonomura, Noriko
• Lundquist, Andrew
• Murén, Eva
• Fels, Max
• Tengvall, Katarina
• Pielberg, Gerli
• Dufaure de Citres, Caroline
• Dorso, Laetitia
• Abadie, Jérôme
• Hanson, Jeanette
• Thomas, Anne
• Leegwater, Peter
• Hedhammar, Åke
• Lindblad-Toh, Kerstin
• Meadows, Jennifer R S
• Wade, Claire

Titel

Thorough investigation of a canine autoinflammatory disease (AID) confirms one main risk locus and suggests a modifier locus for amyloidosis

Ist Teil von

• PloS one, 2013-10, Vol.8 (10), p.e75242-e75242

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• Autoinflammatory disease (AID) manifests from the dysregulation of the innate immune system and is characterised by systemic and persistent inflammation. Clinical heterogeneity leads to patients presenting with one or a spectrum of phenotypic signs, leading to difficult diagnoses in the absence of a clear genetic cause. We used separate genome-wide SNP analyses to investigate five signs of AID (recurrent fever, arthritis, breed specific secondary dermatitis, otitis and systemic reactive amyloidosis) in a canine comparative model, the pure bred Chinese Shar-Pei. Analysis of 255 DNA samples revealed a shared locus on chromosome 13 spanning two peaks of association. A three-marker haplotype based on the most significant SNP (p<2.6×10(-8)) from each analysis showed that one haplotypic pair (H13-11) was present in the majority of AID individuals, implicating this as a shared risk factor for all phenotypes. We also noted that a genetic signature (F ST) distinguishing the phenotypic extremes of the breed specific Chinese Shar-Pei thick and wrinkled skin, flanked the chromosome 13 AID locus; suggesting that breed development and differentiation has played a parallel role in the genetics of breed fitness. Intriguingly, a potential modifier locus for amyloidosis was revealed on chromosome 14, and an investigation of candidate genes from both this and the chromosome 13 regions revealed significant (p<0.05) renal differential expression in four genes previously implicated in kidney or immune health (AOAH, ELMO1, HAS2 and IL6). These results illustrate that phenotypic heterogeneity need not be a reflection of genetic heterogeneity, and that genetic modifiers of disease could be masked if syndromes were not first considered as individual clinical signs and then as a sum of their component parts.