Genome Resequencing for Smyth Line Chicken as Autoimmune Vitiligo Model

The Smyth line (SL) chicken is the only animal model for autoimmune vitiligo that spontaneously displays all clinical and biological manifestations of the human disorder. To understand the genetic component underlying the susceptibility to develop SL vitiligo (SLV), whole genome resequencing analysis was performed in SL chickens with confirmed SLV expression and compared with parental Brown line (BL) chickens, which maintain a very low incidence rate of vitiligo. Illumina sequencing technology and reference based assembly on Red Jungle Fowl genome sequences were used. Results of genome resequencing of pooled DNA of each 10 BL and SL chickens reached 5.1x and 7.0x coverage, respectively, of the Red Jungle Fowl reference chicken genome. Through a series of filtering processes, totally ~1 million unique SNPs were found in SL alone. Eventually 156 reliable marker SNPs, which can induce non-synonymous mutations in amino acid sequences over 139 genes. Bioinformatic study of the 156 most reliable marker SNPs included factors involving dermatological diseases and conditions such as ADAMTS13, ASPM, ATP6V0A2, BRCA2, COL12A1, GRM5, LRP2, OBSCN, PLAU, RNF168, STAB2, and XIRP1. Gene network analysis, which represents the intermolecular connections, revealed that vitiligo development appeared to be associated with the interactions with protein kinases (MAPK, ERK1/2, PKC, PRKDC), phosphatase (PPP1CA), ubiquitinylation (UBC) and amyloid production (APP). The genetic markers and bioinformatics interpretations of amino acid mutation found in SLV chickens may provide insight into the genetic component responsible for the progression of autoimmune vitiligo. This work was supported by Arkansas Bioscience Institute and Arkansas Agricultural Experimental Station.