Provided by the author(s) and NUI Galway in accordance with publisher policies. Please cite the published version when available. Title Genomic and transcriptomic investigations into the feed efficiency phenotype of beef cattle Author(s) Higgins, Marc Publication Date 2019-03-06 Publisher NUI Galway Item record http://hdl.handle.net/10379/15008 Downloaded 2021-09-25T18:07:39Z Some rights reserved. For more information, please see the item record link above. Genomic and Transcriptomic Investigations into the Feed Efficiency Phenotype of Beef Cattle Marc Higgins, B.Sc., M.Sc. A thesis submitted for the Degree of Doctor of Philosophy to the Discipline of Biochemistry, School of Natural Sciences, National University of Ireland, Galway. Supervisor: Dr. Derek Morris Discipline of Biochemistry, School of Natural Sciences, National University of Ireland, Galway. Supervisor: Dr. Sinéad Waters Teagasc, Animal and Bioscience Research Department, Animal & Grassland Research and Innovation Centre, Teagasc, Grange. Submitted November 2018 Table of Contents Declaration ................................................................................................................ vii Funding .................................................................................................................... viii Acknowledgements .................................................................................................... ix Abstract ....................................................................................................................... x List of Tables ............................................................................................................ xii List of Supplementary Tables ................................................................................ xiii List of Figures .......................................................................................................... xiv List of Supplementary Figures ................................................................................ xv List of Appendices ................................................................................................... xvi List of Abbreviations ............................................................................................. xvii Chapter 1 ................................................................................................................ 1 1. Introduction ............................................................................................................ 2 1.1. The increasing global demand for beef ............................................................. 2 1.2.1. How can Irish beef meet increasing global food demands ........................... 3 1.3. Feed efficiency and its measures ........................................................................ 4 1.3.1. Residual feed intake ......................................................................................... 5 1.3.2. Statistical calculation of RFI ........................................................................... 6 1.3.3. RFI measurement trial .................................................................................... 7 1.3.4. Effect of breed on RFI ..................................................................................... 8 1.3.5. Heritability of RFI ........................................................................................... 8 1.3.6. Repeatability of RFI in beef cattle .................................................................. 8 1.4. Physiological basis for RFI variation .............................................................. 10 1.4.1. The impact of feeding behaviour on RFI ..................................................... 10 1.4.2. Activity levels and feed efficiency ................................................................. 11 1.4.3. Appetite and RFI ............................................................................................ 11 1.4.4. Digestion of consumed feed and the role of the rumen in RFI .................. 13 i 1.4.5. Methane production and RFI ....................................................................... 14 1.4.6. Body composition and its effect on RFI ....................................................... 15 1.4.7. The impact of body maintenance on RFI ..................................................... 16 1.4.7.1. Energy consumption of the gastrointestinal tract and liver .................... 16 1.4.7.2. Maintenance and metabolism of skeletal muscle ..................................... 17 1.4.8. The role of lipid metabolism in feed efficiency ............................................ 17 1.4.9. Mitochondria and energetic efficiency ......................................................... 18 1.4.10. Blood metabolites and feed efficiency ........................................................ 18 1.4.11. Stress physiology and feed efficiency.......................................................... 19 1.5. The genome and genomics ................................................................................ 20 1.5.1. The Bovine Genome Project .......................................................................... 20 1.5.2. Variation in the bovine genome .................................................................... 21 1.5.3. Genome-wide association studies .................................................................. 21 1.5.3.1. GWAS for feed efficiency ........................................................................... 22 1.5.3.2. Uncovering selection markers applicable to multiple breeds ................. 27 1.5.4. Next-generation sequencing .......................................................................... 28 1.5.5. Bioinformatics ................................................................................................ 30 1.5.6. Transcriptomics ............................................................................................. 30 1.5.6.1. Microarrays ................................................................................................. 32 1.5.6.2. RNA-Seq ...................................................................................................... 32 1.5.6.3. RNA-Seq of RFI-divergent cattle .............................................................. 33 1.5.6.4. How differentially expressed genes can aid in genomic selection ........... 38 1.5.7. Expression quantitative trait loci analysis for genomic selection .............. 38 1.5.8. Network Biology ............................................................................................. 40 1.6. The Irish national cattle selection programme ............................................... 42 1.6.1. Genomic selection ........................................................................................... 43 1.6.1.1. Genomic selection in Ireland ...................................................................... 44 ii 1.6.1.2. Genomic selection in beef cattle ................................................................. 44 1.6.1.3. Genomic selection for RFI .......................................................................... 45 1.7. Aims and objectives .......................................................................................... 45 Chapter 2 .............................................................................................................. 48 Preamble to Chapter 2: Statement of contribution .......................................... 49 2. GWAS and eQTL analysis identifies a SNP associated with both residual feed intake and GFRA2 expression in beef cattle. ......................................................... 50 2.1. Abstract .............................................................................................................. 51 2.2. Introduction ....................................................................................................... 51 2.3. Materials and methods ..................................................................................... 54 2.3.1. Phenotypic data collation .............................................................................. 54 2.3.2. Genotyping ...................................................................................................... 56 2.3.3. Preparation of files for analysis .................................................................... 57 2.3.4. Genome-wide association studies .................................................................. 58 2.3.5. Meta-Analysis ................................................................................................. 58 2.3.6. Validation of internationally identified RFI SNPs in Irish beef cattle ...... 58 2.3.7. Functional annotation of genes ..................................................................... 58 2.3.8. eQTL analysis ................................................................................................. 59 2.4.2. GWAS and meta-analysis for ADG .............................................................. 64 2.4.3. GWAS and meta-analysis for FI ................................................................... 66 2.4.4. Validation of internationally identified SNPs in Irish cattle ...................... 68 2.4.5. eQTL analysis of SNPs identified as significant from meta-analysis ........ 68 2.5. Discussion ........................................................................................................... 70 2.6. Conclusion .........................................................................................................