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Published VersionCC BY V4.0, Open Access
Journal article
An ancient haplotype containing antimicrobial peptide gene variants is associated with severe fungal skin disease in Persian cats
PLoS Genetics, Vol.18(2), pp.1-18
2022
PMID: 35157719
Abstract
Dermatophytosis, also known as ringworm, is a contagious fungal skin disease affecting humans and animals worldwide. Persian cats exhibit severe forms of the disease more commonly than other breeds of cat, including other long-haired breeds. Certain types of severe dermatophytosis in humans are reportedly caused by monogenic inborn errors of immunity. The goal of this study was to identify genetic variants in Persian cats contributing to the phenotype of severe dermatophytosis. Whole-genome sequencing of case and control Persian cats followed by a genome-wide association study identified a highly divergent, disease-associated haplotype on chromosome F1 containing the S100 family of genes. S100 calcium binding protein A9 (S100A9), which encodes a subunit of the antimicrobial heterodimer known as calprotectin, contained 13 nonsynonymous variants between cases and controls. Evolutionary analysis of S100A9 haplotypes comparing cases, controls, and wild felids suggested the divergent disease-associated haplotype was likely introgressed into the domestic cat lineage and maintained via balancing selection. We demonstrated marked upregulation of calprotectin expression in the feline epidermis during dermatophytosis, suggesting involvement in disease pathogenesis. Given this divergent allele has been maintained in domestic cat and wildcat populations, this haplotype may have beneficial effects against other pathogens. The pathogen specificity of this altered protein should be investigated before attempting to reduce the allele frequency in the Persian cat breed. Further work is needed to clarify if severe Persian dermatophytosis is a monogenic disease or if hidden disease-susceptibility loci remain to be discovered. Consideration should be given to engineering antimicrobial peptides such as calprotectin for topical treatment of dermatophytosis in humans and animals.
Details
- Title
- An ancient haplotype containing antimicrobial peptide gene variants is associated with severe fungal skin disease in Persian cats
- Authors
- Alexandra N Myers (Corresponding Author) - Texas A&M UniversitySara D Lawhon (Author) - Texas A&M UniversityAlison B Diesel (Author) - Texas A&M UniversityCharles W Bradley (Author) - University of PennsylvaniaAline Rodrigues Hoffmann (Author) - Texas A&M UniversityWilliam J Murphy (Author) - Texas A&M University99 Lives Cat Genome Consortium (Research Group)Robert Harvey (Consortium Member) - University of the Sunshine Coast, Queensland, School of Health
- Publication details
- PLoS Genetics, Vol.18(2), pp.1-18
- Publisher
- Public Library of Science
- Date published
- 2022
- DOI
- 10.1371/journal.pgen.1010062
- ISSN
- 1553-7404
- PMID
- 35157719
- Copyright note
- © 2022 Myers et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- Grant note
- This work was supported by a grant from the EveryCat Health Foundation, MT16-015 (A.R.H. and W.J.M) (https://everycat.org/), and partially supported by a grant from the Morris Animal Foundation, D19FE-004 (W.J.M.) (https://www.morrisanimalfoundation.org/). A.N.M. was supported by a National Institutes of Health postdoctoral training fellowship, T32OD011083 (https://www.nih.gov).
- Organisation Unit
- School of Health
- Language
- English
- Record Identifier
- 99982892502621
- Output Type
- Journal article
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