Data from: Genome-Wide Analyses Suggest Mechanisms Involving Early B-Cell Development in Canine IgA Deficiency

Immunoglobulin A deficiency (IgAD) is the most common primary immune
deficiency disorder in both humans and dogs, characterized by recurrent
mucosal tract infections and a predisposition for allergic and other
immune mediated diseases. In several dog breeds, low IgA levels have been
observed at a high frequency and with a clinical resemblance to human
IgAD. In this study, we used genome-wide association studies (GWAS) to
identify genomic regions associated with low IgA levels in dogs as a
comparative model for human IgAD. We used a novel percentile
groups-approach to establish breed-specific cut-offs and to perform
analyses in a close to continuous manner. GWAS performed in four breeds
prone to low IgA levels (German shepherd, Golden retriever, Labrador
retriever and Shar-Pei) identified 35 genomic loci suggestively associated
(p <0.0005) to IgA levels. In German shepherd, three genomic
regions (candidate genes include KIRREL3 and SERPINA9) were genome-wide
significantly associated (p <0.0002) with IgA levels. A ~20kb long
haplotype on CFA28, significantly associated (p = 0.0005) to IgA levels in
Shar-Pei, was positioned within the first intron of the gene SLIT1. Both
KIRREL3 and SLIT1 are highly expressed in the central nervous system and
in bone marrow and are potentially important during B-cell development.
SERPINA9 expression is restricted to B-cells and peaks at the time-point
when B-cells proliferate into antibody-producing plasma cells. The
suggestively associated regions were enriched for genes in Gene Ontology
gene sets involving inflammation and early immune cell development.