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Genome-wide analysis in German shepherd dogs reveals association of a locus on CFA 27 with atopic dermatitis.

Tengvall K, Kierczak M, Bergvall K, Olsson M, Frankowiack M, Farias FH, Pielberg G, Carlborg Ö, Leeb T, Andersson G, Hammarström L, Hedhammar Å, Lindblad-Toh K - PLoS Genet. (2013)

Bottom Line: Disease prevalence differed significantly between the subpopulations contributing to population stratification (λ = 1.3), which was successfully corrected for using a mixed model approach.The total associated region was defined as a ~1.5-Mb-long haplotype including eight genes.Our results may yield further insight into the genetics behind both canine and human AD.

View Article: PubMed Central - PubMed

Affiliation: Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. katarina.tengvall@imbim.uu.se

ABSTRACT
Humans and dogs are both affected by the allergic skin disease atopic dermatitis (AD), caused by an interaction between genetic and environmental factors. The German shepherd dog (GSD) is a high-risk breed for canine AD (CAD). In this study, we used a Swedish cohort of GSDs as a model for human AD. Serum IgA levels are known to be lower in GSDs compared to other breeds. We detected significantly lower IgA levels in the CAD cases compared to controls (p = 1.1 × 10(-5)) in our study population. We also detected a separation within the GSD cohort, where dogs could be grouped into two different subpopulations. Disease prevalence differed significantly between the subpopulations contributing to population stratification (λ = 1.3), which was successfully corrected for using a mixed model approach. A genome-wide association analysis of CAD was performed (n cases = 91, n controls = 88). IgA levels were included in the model, due to the high correlation between CAD and low IgA levels. In addition, we detected a correlation between IgA levels and the age at the time of sampling (corr = 0.42, p = 3.0 × 10(-9)), thus age was included in the model. A genome-wide significant association was detected on chromosome 27 (praw = 3.1 × 10(-7), pgenome = 0.03). The total associated region was defined as a ~1.5-Mb-long haplotype including eight genes. Through targeted re-sequencing and additional genotyping of a subset of identified SNPs, we defined 11 smaller haplotype blocks within the associated region. Two blocks showed the strongest association to CAD. The ~209-kb region, defined by the two blocks, harbors only the PKP2 gene, encoding Plakophilin 2 expressed in the desmosomes and important for skin structure. Our results may yield further insight into the genetics behind both canine and human AD.

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Related in: MedlinePlus

A mixed model corrected sufficiently for the population stratification.Quantile-Quantile (QQ) plot from the association analysis using the mixed model approach.
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pgen-1003475-g002: A mixed model corrected sufficiently for the population stratification.Quantile-Quantile (QQ) plot from the association analysis using the mixed model approach.

Mentions: We used the mixed model approach to account for the observed population structure and cryptic relatedness between the individuals, which is common in dog breeds. After fitting the mixed model we observed no inflation (λ = 1.0) as presented in quantile-quantile (QQ) plot (Figure 2).


Genome-wide analysis in German shepherd dogs reveals association of a locus on CFA 27 with atopic dermatitis.

Tengvall K, Kierczak M, Bergvall K, Olsson M, Frankowiack M, Farias FH, Pielberg G, Carlborg Ö, Leeb T, Andersson G, Hammarström L, Hedhammar Å, Lindblad-Toh K - PLoS Genet. (2013)

A mixed model corrected sufficiently for the population stratification.Quantile-Quantile (QQ) plot from the association analysis using the mixed model approach.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3649999&req=5

pgen-1003475-g002: A mixed model corrected sufficiently for the population stratification.Quantile-Quantile (QQ) plot from the association analysis using the mixed model approach.
Mentions: We used the mixed model approach to account for the observed population structure and cryptic relatedness between the individuals, which is common in dog breeds. After fitting the mixed model we observed no inflation (λ = 1.0) as presented in quantile-quantile (QQ) plot (Figure 2).

Bottom Line: Disease prevalence differed significantly between the subpopulations contributing to population stratification (λ = 1.3), which was successfully corrected for using a mixed model approach.The total associated region was defined as a ~1.5-Mb-long haplotype including eight genes.Our results may yield further insight into the genetics behind both canine and human AD.

View Article: PubMed Central - PubMed

Affiliation: Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. katarina.tengvall@imbim.uu.se

ABSTRACT
Humans and dogs are both affected by the allergic skin disease atopic dermatitis (AD), caused by an interaction between genetic and environmental factors. The German shepherd dog (GSD) is a high-risk breed for canine AD (CAD). In this study, we used a Swedish cohort of GSDs as a model for human AD. Serum IgA levels are known to be lower in GSDs compared to other breeds. We detected significantly lower IgA levels in the CAD cases compared to controls (p = 1.1 × 10(-5)) in our study population. We also detected a separation within the GSD cohort, where dogs could be grouped into two different subpopulations. Disease prevalence differed significantly between the subpopulations contributing to population stratification (λ = 1.3), which was successfully corrected for using a mixed model approach. A genome-wide association analysis of CAD was performed (n cases = 91, n controls = 88). IgA levels were included in the model, due to the high correlation between CAD and low IgA levels. In addition, we detected a correlation between IgA levels and the age at the time of sampling (corr = 0.42, p = 3.0 × 10(-9)), thus age was included in the model. A genome-wide significant association was detected on chromosome 27 (praw = 3.1 × 10(-7), pgenome = 0.03). The total associated region was defined as a ~1.5-Mb-long haplotype including eight genes. Through targeted re-sequencing and additional genotyping of a subset of identified SNPs, we defined 11 smaller haplotype blocks within the associated region. Two blocks showed the strongest association to CAD. The ~209-kb region, defined by the two blocks, harbors only the PKP2 gene, encoding Plakophilin 2 expressed in the desmosomes and important for skin structure. Our results may yield further insight into the genetics behind both canine and human AD.

Show MeSH
Related in: MedlinePlus