Abstract

Background

   Genome-wide association studies (GWAS) are extensively used to identify
   single nucleotide polymorphisms (SNP) underlying the genetic variation
   of complex traits. However, much uncertainly often still exists about
   the causal variants and genes at quantitative trait loci (QTL). The aim
   of this study was to identify QTL associated with residual feed intake
   (RFI) and genes in these regions whose expression is also associated
   with this trait. Angus cattle (2190 steers) with RFI records were
   genotyped and imputed to high density arrays (770 K) and used for a
   GWAS approach to identify QTL associated with RFI. RNA sequences from
   126 Angus divergently selected for RFI were analyzed to identify the
   genes whose expression was significantly associated this trait with
   special attention to those genes residing in the QTL regions.

Results

   The heritability for RFI estimated for this Angus population was 0.3.
   In a GWAS, we identified 78 SNPs associated with RFI on six QTL (on
   BTA1, BTA6, BTA14, BTA17, BTA20 and BTA26). The most significant SNP
   was found on chromosome BTA20 (rs42662073) and explained 4% of the
   genetic variance. The minor allele frequencies of significant SNPs
   ranged from 0.05 to 0.49. All regions, except on BTA17, showed a
   significant dominance effect. In 1 Mb windows surrounding the six
   significant QTL, we found 149 genes from which OAS2, STC2, SHOX, XKR4,
   and SGMS1 were the closest to the most significant QTL on BTA17, BTA20,
   BTA1, BTA14, and BTA26, respectively. In a 2 Mb windows around the six
   significant QTL, we identified 15 genes whose expression was
   significantly associated with RFI: BTA20) NEURL1B and CPEB4; BTA17)
   RITA1, CCDC42B, OAS2, RPL6, and ERP29; BTA26) A1CF, SGMS1, PAPSS2, and
   PTEN; BTA1) MFSD1 and RARRES1; BTA14) ATP6V1H and MRPL15.

Conclusions

   Our results showed six QTL regions associated with RFI in a beef Angus
   population where five of these QTL contained genes that have expression
   associated with this trait. Therefore, here we show that integrating
   information from gene expression and GWAS studies can help to better
   understand the genetic mechanisms that determine variation in complex
   traits.

   Keywords: Residual feed intake, GWAS, QTL, RNA-seq, Gene expression,
   Angus, Beef cattle

Background

   The incorporation of genomic information in livestock breeding programs
   is a common strategy to improve accuracy of selection for economically
   important traits. This is most useful for traits in the breeding
   objective that are not often measured by breeders. In beef cattle, the
   aim of most production systems is to select for more feed efficient
   animals since feed costs constitute around 70% of the total expenses
   [[35]1]. The measurement of feed intake is costly, usually requiring
   expensive equipment to determine phenotypes for growth and feed intake
   in a 70 days test period in a feedlot. Feed efficiency in beef cattle
   is often expressed as residual feed intake (RFI) which is the
   difference between the observed feed intake recorded over a period of
   time and the expected feed intake based on the animal’s growth rate and
   maintenance requirement [[36]2]. RFI reflects the variation in feed
   intake conditional on productivity, and therefore the variation in RFI
   can be used to explore the underlying causes of genetic variation using
   genomic technologies.

   Modern genomic tools can be utilised to unravel the underlying biology
   of genetic variability in plants and animals. Methods that examine the
   heritability of traits, along with genome-wide association and gene
   expression studies have been utilised to attempt to understand the
   genetic basis underlying phenotypic differences between individuals.
   Numerous studies have reported variance components and heritabilities
   for RFI in cattle and correlations with other important production
   traits [[37]3–[38]5]. More recently, genome-wide association studies
   (GWAS) have been used to reveal the genomic architecture of polygenic
   traits by finding statistical associations between the phenotype and
   genetic markers assumed close to putative QTL (quantitative trait
   loci). Several GWAS for RFI have been performed in beef and dairy
   cattle [[39]6–[40]10]. Estimates of heritability of RFI range from low
   to moderate (0.14 to 0.49) and GWAS point at QTL for this trait in
   regions on many chromosomes (BTA3, BTA5, BTA6, BTA8, BTA12, BTA13,
   BTA15, BTA17, BTA18, BTA20, BTA21 and BTA22, see references [41]6,