01591: Identification of the Genes That Confer Risk for Atopic Dermatitis

Grant Status: Closed

Grant Amount: $107,133
Natasha J Olby, VetMB PhD; North Carolina State University
January 1, 2012 - December 31, 2013

Sponsor(s): Westie Foundation of America, Inc.

Breed(s): West Highland White Terrier
Research Program Area: Dermatology and Allergic Disease
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Project Summary

186 WHWTs (97 affected and 89 normal) were genotyped on the high density Illumina SNP chip that gives very good coverage of the whole genome. Data from these dogs was used to perform association studies to determine whether there was a significant association between affected phenotype (clinical signs) and a particular chromosomal region. These analyses can be greatly influenced by relatedness between dogs and by other factors that affect sampling bias. Evaluation of population structure revealed significant issues that required correction. However, after correction for population structure, we identified a region on chromosome 3 that has a significant association with atopic dermatitis, and sequenced two candidate genes in this region. Both genes were normal in affected dogs. Our results throw into question recent publications by other groups on the genetic basis of this disease and highlight the importance of controlling for population structure when performing the analysis. We have now sequenced the entire genome of two affected and two normal dogs in order to investigate the regions we identified in our study further. Initial data analysis did not reveal obvious candidates but the control population to which the dogs were compared was not optimal. The analysis is being repeated with more stringent control criteria and work on this extremely large dataset will be ongoing, with the ability to investigate any new published variants for canine atopic dermatitis immediately.

Publication(s)

Tengvall, K., Sundström, E., Wang, C. et al. Bayesian model and selection signature analyses reveal risk factors for canine atopic dermatitis. Commun Biol 5, 1348 (2022). https://doi.org/10.1038/s42003-022-04279-8

Agler, C. S., Friedenberg, S., Olivry, T., Meurs, K. M., & Olby, N. J. (2019). Genome-wide association analysis in West Highland White Terriers with atopic dermatitis. Veterinary Immunology and Immunopathology, 209, 1–6. https://doi.org/10.1016/j.vetimm.2019.01.004
 
Salzmann, C. A., Olivry, T. J., Nielsen, D. M., Paps, J. S., Harris, T. L., & Olby, N. J. (2011). Genome-wide linkage study of atopic dermatitis in West Highland White Terriers. BMC Genetics, 12(1), 37. https://doi.org/10.1186/1471-2156-12-37

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