SNP prioritization in targeted sequencing data associated with humoral immune responses in chicken

Poult Sci. 2021 Aug 19;100(11):101433. doi: 10.1016/j.psj.2021.101433. Online ahead of print.

Abstract

Our study aimed to identify single nucleotide polymorphisms (SNPs) with a significant impact on the innate immunity represented by antibody response against lipopolysaccharide (LPS) and lipoteichoid acid (LTA) and the adaptive immune response represented toward keyhole limpet hemocyanin (KLH) using the SNP prioritization method. Data set consisted of 288 F2 experimental individuals, created by crossing Green-legged Partridgelike and White Leghorn. The analyzed SNPs were located within 24 short genomic regions of GGA1, GGA2, GGA3, GGA4, GGA9, GGA10, GGA14, GGA18, and GGZ, pre-targeted based on literature references and database information. For the specific antibody response toward KLH at d 0 the most highly prioritized SNP for additive and dominance effects were located on GGA2 in the 3'UTR of MYD88. For the response at d 7, the most highly prioritized SNP pointed at the 3'UTR of MYD88, but potential causal additive variants were located within ADIPOQ and one in PROCR. The highest priority for additive and dominance effects in the antibody response toward lipoteichoic acid at d 0 was attributed to the same SNP, located on GGA2 in the 3'UTR region of MYD88. Two SNPs among the top-10 for additive effect were located in the exon of NOCT. SNPs selected for their additive effect on antibody response toward lipopolysaccharide at d 0 marked 3 genes - NOCT, MYD88, and SNX8, while SNPs selected for their dominance effect marked - NOCT, ADIPOQ, and MYD88. The top-10 variants identified in our study were located in different functional parts of the genome. In the context of causality three groups can be distinguished: variants located in exons of protein coding genes (ADIPOQ, NOCT, PROCR, SNX8), variants within exons of non-coding transcripts, and variants located in genes' UTR regions. Variants from the first group influence protein structure and variants from both latter groups' exhibit regulatory roles on DNA (UTR) or RNA (lncRNA).

Keywords: adaptive immunity; amplicon; innate immunity; mixed model.