An Expression QTL of Closely Linked Candidate Genes Affects pH of Meat in Chickens

Abstract

Genetical genomics has been suggested as a powerful approach to study the genotype-phenotype gap. However, the relatively low power of these experiments (usually related to the high cost) has hindered fulfillment of its promise, especially for loci (QTL) of moderate effects.One strategy with which to overcome the issue is to use a targeted approach. It has two clear advantages: (i) it reduces the problem to a simple comparison between different genotypic groups at the QTL and (ii) it is a good starting point from which to investigate downstream effects of the QTL. In this study, from 698 F2 birds used for QTL mapping, gene expression profiles of 24 birds with divergent homozygous QTL genotypes were investigated. The targeted QTL was on chromosome 1 and affected initial pH of breast muscle. The biological mechanisms controlling this trait can be similar to those affecting malignant hyperthermia or muscle fatigue in humans. The gene expression study identified 10 strong local signals that were markedly more significant compared to any genes on the rest of the genome. The differentially expressed genes all mapped to a region ,1 Mb, suggesting a remarkable reduction of the QTL interval. These results, combined with analysis of downstream effect of the QTL using gene network analysis, suggest that the QTL is controlling pH by governing oxidative stress. The results were reproducible with use of as few as four microarrays on pooled samples (with lower significance level). The results demonstrate that this cost-effective approach is promising for characterization of QTL. EXISTING genetic variation provides a valuable resource for dissection of the genetic architecture of complex traits. Despite rapid developments in genetic and genomic tools, fine dissection of complex traits has remained challenging (Ron and Weller 2007). Many genetic studies have successfully mapped and identified chromosomal regions controlling these traits, but very few succeeded in further characterization and identification of genes and causative mutations. The extent to which protein-coding changes vs. regulatory changes contribute to the variation in complex traits is not clear. However, much of the naturally occurring variation in complex traits is believed to be partially controlled by regulatory elements. Changes in these regulatory elements, either at a single nucleotide level or more complex structural changes in the region, may underlie variations in gene expression (Guryev et al. 2008). Since its formal description (Jansen and Nap 2001), genetical genomics, the combined use of genetic mapping and expression profile (or other genomic information) in segregating populations, has shown to have great potential in addressing the issue. However, the successes to date do not match the original promise. One of the main reasons is the low power of the experiments linked to the low sample size due to high cost of such experiments, especially the genomic part of the study (De Koning and Haley 2005). One of the solutions proposed to address...

Using targeted re-sequencing for identification of candidate genes and SNPs for a QTL affecting the pH value of chicken meat

“…Therefore, oxidative stress has been suggested to contribute to the pH15 value of chicken meat (Nadaf et al 2014). Interestingly, PRDX4, as one member of the antioxidant enzyme family, plays a crucial role in the process of protecting muscle cells against oxidative stress (Novelli et al 1991;Leyens et al 2003).…”

“…In this study, we selected 10 birds from the F2 with inferred QTL genotypes of QQ (5 birds, homozygous for HG line alleles) or qq (5 birds, homozygous for LG line alleles). The selected individuals are a subset of the birds that were used for the targeted genetical genomics study by Nadaf et al (2014).…”

“…Detecting potential causative genes and SNPs corresponding to the genotypic differences between two genotype groups. The QTL region affecting the pH15 value of chicken meat has been previously fine mapped (Nadaf et al 2014). Although QTL analysis has been shown to be useful to detect the genetic variations related to the common complex trait and genotype, the ability to detect the causative functional genes and SNPs is scarce.…”

“…Therefore, pre-slaughter stress may be associated with variation in the initial rate of drop in pH (Chabault et al, 2012). At the genetic level, a recent fine mapping study has identified a QTL region affecting muscle pH measured 15 minutes post-mortem (pH15) using an F 2 intercross between High Growth (HG) and Low Growth (LG) chicken lines (Nadaf et al 2007(Nadaf et al , 2014. The HG and LG lines are being bi-directionally selected on body weight at nine week of age, where the HG lines show lower pH15 values and the LG lines show higher pH15 values.…”

“…In this study, ten birds that were homozygous at the targeted QTL (QQ vs. qq) were selected for re-sequencing, where QQ corresponds to alleles from the HG lines and qq corresponds to alleles from the LG lines (Nadaf et al 2014). Based on the bioinformatics analysis of the mapped QTL region and SNPs detected by Next Generation Sequencing (NGS) data, we report a number of candidate genes and SNPs.…”