Canine major histocompatibility complex class I (MHC-I) diversity landscape

Area of Science:

• Immunogenetics
• Comparative Genomics

Background:

• Major Histocompatibility Complex class I (MHC-I) genes are crucial for immunology and exhibit high diversity.
• Understanding canine MHC-I diversity is vital as dogs are a key translational model, yet this landscape is poorly understood compared to humans.

Approach:

• Utilized a newly developed software, KPR de novo assembler and genotyper, to genotype 1,325 dog samples (1,025 dogs) with paired-end RNA-seq data.
• Performed extensive quality control, genotyping 926 dogs and identifying 97 known and 52 putative new MHC-I alleles.

Key Points:

• Identified 97 known and 52 putative new canine MHC-I alleles across 926 dogs.
• DLA-I gene expression varied by tissue, with lowest levels in testis and brain, and highest in blood, corpus luteum, and spleen.
• Discovered dominant, breed-specific, and mutually co-occurring/exclusive alleles within the canine population.

Conclusions:

• Canine DLA-88 exhibits population-level diversity comparable to human HLA-A/B/C, but lower within-breed diversity.
• 80% of hypervariable regions in canine and human MHC-I alleles overlap, with most interacting with peptides.
• This research provides critical insights for canine immunology and translational research.