An ancient haplotype containing antimicrobial peptide gene variants is associated with severe fungal skin disease in Persian cats

• DOI: 10.1371/journal.pgen.1010062
• Publication Date: 2022-02-14T19:00:00Z
• Authors: Alexandra N. Myers; Sara D. Lawhon; Alison B. Diesel; Charles W. Bradley; Aline Rodrigues H...; William J. Murphy
• Keywords: 0301 basic medicine; QH426-470; Skin Diseases; 03 medical and health sciences; Haplotypes; Tinea; Genetics; Cats; Animals; Leukocyte L1 Antigen Complex; Antimicrobial Peptides; Research Article; Genome-Wide Association Study

Dermatophytosis, also known as ringworm, is a contagious fungal skin disease affecting humans and animals worldwide. Persian cats exhibit severe forms of the more commonly than other breeds cat, including long-haired breeds. Certain types dermatophytosis in are reportedly caused by monogenic inborn errors immunity. The goal this study was to identify genetic variants contributing phenotype dermatophytosis. Whole-genome sequencing case control followed genome-wide association identified highly divergent, disease-associated haplotype on chromosome F1 containing S100 family genes. calcium binding protein A9 ( S100A9 ), which encodes subunit antimicrobial heterodimer calprotectin, contained 13 nonsynonymous between cases controls. Evolutionary analysis haplotypes comparing cases, controls, wild felids suggested divergent likely introgressed into domestic cat lineage maintained via balancing selection. We demonstrated marked upregulation calprotectin expression feline epidermis during dermatophytosis, suggesting involvement pathogenesis. Given allele has been wildcat populations, may have beneficial effects against pathogens. pathogen specificity altered should be investigated before attempting reduce frequency breed. Further work needed clarify if or hidden disease-susceptibility loci remain discovered. Consideration given engineering peptides such for topical treatment animals.