Strong selection signatures for Aleutian disease tolerance acting on novel candidate genes linked to immune and cellular responses in American mink (Neogale vison)

Abstract

Aleutian disease (AD) is a multi-systemic infectious disease in American mink (Neogale vison) caused by Aleutian mink disease virus (AMDV). This study aimed to identify candidate regions and genes underlying selection for response against AMDV using whole-genome sequence (WGS) data. Three case-control selection signatures studies were conducted between animals (N = 85) producing high versus low antibody levels against AMDV, grouped by counter immunoelectrophoresis (CIEP) test and two enzyme-linked immunosorbent assays (ELISA). Within each study, selection signals were detected using fixation index (FST) and nucleotide diversity (θπ ratios), and validated by cross-population extended haplotype homozygosity (XP-EHH) test. Within- and between-studies overlapping results were then evaluated. Within-studies overlapping results indicated novel candidate genes related to immune and cellular responses (e.g., TAP2, RAB32), respiratory system function (e.g., SPEF2, R3HCC1L), and reproduction system function (e.g., HSF2, CFAP206) in other species. Between-studies overlapping results identified three large segments under strong selection pressure, including two on chromosome 1 (chr1:88,770-98,281 kb and chr1:114,133-120,473) and one on chromosome 6 (chr6:37,953-44,279 kb). Within regions with strong signals, we found novel candidate genes involved in immune and cellular responses (e.g., homologous MHC class II genes, ITPR3, VPS52) in other species. Our study brings new insights into candidate regions and genes controlling AD response.

Figure 1

Red, blue, and green layers of circus plot show the distribution of (Z_(fst)), log₂(θπ ratios), and -log_10(p-value) of XP-EHH values, respectively. These values were calculated using a sliding window approach between animals grouped as cases and controls using CIEP test (A), VP2 ELISA (B), and AMDVG ELISA (C) records.

Figure 2

Venn diagrams of within-studies overlapping genomic windows, among top 1% regions obtained from Z_(FST) and log_{2(θπ ratios)} tests and the significant regions (q-value < 0.05) identified by XP-EHH test. Signatures of selection studies were applied between animals grouped as cases and controls using CIPE test (A), VP2 ELISA (B), and AMDVG ELISA (C) records.

Figure 3

Graphical visualization of the American mink chromosomes depicting overlapping within- (A) and between-studies (B) genomic regions underlying selection pressure.

Figure 4

Venn diagram of between-studies overlapping genomic regions (A) and candidate genes (B). The genomic regions highlighted in blue color represent segments on chromosome 1 overlapping with homologous human (HLA) and rabbit (RLA) leukocyte antigen genes loci (chr1:119,357–119,996 kb).