Functional classification of 15 million SNPs detected from diverse chicken populations

Abstract

Next-generation sequencing has prompted a surge of discovery of millions of genetic variants from vertebrate genomes. Besides applications in genetic association and linkage studies, a fraction of these variants will have functional consequences. This study describes detection and characterization of 15 million SNPs from chicken genome with the goal to predict variants with potential functional implications (pfVars) from both coding and non-coding regions. The study reports: 183K amino acid-altering SNPs of which 48% predicted as evolutionary intolerant, 13K splicing variants, 51K likely to alter RNA secondary structures, 500K within most conserved elements and 3K from non-coding RNAs. Regions of local fixation within commercial broiler and layer lines were investigated as potential selective sweeps using genome-wide SNP data. Relationships with phenotypes, if any, of the pfVars were explored by overlaying the sweep regions with known QTLs. Based on this, the candidate genes and/or causal mutations for a number of important traits are discussed. Although the fixed variants within sweep regions were enriched with non-coding SNPs, some non-synonymous-intolerant mutations reached fixation, suggesting their possible adaptive advantage. The results presented in this study are expected to have important implications for future genomic research to identify candidate causal mutations and in poultry breeding.

Characterization and expression of non‐polymorphic liver expressed antimicrobial peptide 2: LEAP‐2 in the Japanese quail, Coturnix japonica

“…Four non‐synonymous SNPs of LEAP‐2 mature peptide region were reported in 243 chickens from 24 lines (Gheyas et al . ). However, these non‐synonymous SNPs include two frameshift mutations: the amino acid at position 48 changed from proline to serine, which is only found in proline residues in birds, and that at 75 changed from serine to proline, which is highly conserved in birds (Fig.…”

“…This could be attributed to the fact that these SNPs were very rare in birds, or to sequence error, which was analyzed by a next‐generation sequencer and included in two frameshift mutations (Gheyas et al . ). In the six strains of Japanese quail used in this study, it has been reported that there are polymorphisms in the CD1 (Yokoyama et al .…”

“…The non‐synonymous SNPs of GgLEAP‐2 have been registered in dbSNP (Gheyas et al . ), as aforementioned for human and cattle LEAP‐2 . The GgLEAP‐2 homolog is approximately 60% homologous to its mammalian counterparts and has a high degree of homology, found mainly in the C‐terminal part of the mature peptide (Lynn et al .…”

Accumulation of genetic variants associated with immunity in the selective breeding of broilers

“…These variants include N174H and D466H, both found in the leucine-rich surface that is responsible for recognizing and binding double stranded viral RNA and activating innate immunity. When viewed in the context of other mutations that alter charge (D19V, K43Q, R266S, E283G), we hypothesize that the sensitivity of TLR3 to double stranded viral 14 components could be diminished. This decrease in functional efficacy could be physiologically important for growth performance, for example, a mouse knock out of a toll-like receptor (TLR5) has previously been shown to modulate gut microbiome characteristic of obesity and other metabolic disorders [39].…”

“…Such sweeps have revealed the fixation of alleles predicted to be beneficial. For example, specific alleles of the gene encoding thyroid stimulating hormone receptor (TSHR), which is critical for proper metabolic regulation and reproduction, have been shown to be fixed in all modern chickens, but not in the genomes of the Red Jungle Fowl [10,13,14] or chickens dating from ~280 B.C. to ~1700 A.D [13].…”