Transcriptional variation in muscle from cattle with alternative NCAPG/LCORL QTL genotypes

The NCAPG/LCORL locus is a major QTL on bovine chromosome 6 (BTA6) that influences growth and composition in cattle. Genetic variation at this locus is associated with alterations in the developmental program of individuals throughout life that may be detected through transcriptional variation. Here, we propose to characterize how the landscape of transcriptomes differ between individuals with alternative NCAPG/LCORL haplotypes/genotypes. Charolais calves (n=804) were genotyped using the Illumina® BovSNP50 BeadChip and their sires (n=38) were genotyped with the BovineHD BeadChip. Additionally, 53 calves were genotyped on the BovineHD BeadChip (770k) platform for use in further analyses. The 38 sires and 53 calves genotyped on the 770k platform were used to impute the calf genotypes, resulting in approximately 638,230 markers per individual used for GWAS analyses. Twenty-four animals were selected based on alternative homozygous NCAPG/LCORL haplotypes/genotypes (i.e. 12 “QQ” and 12 “qq”, where “Q” is the QTL allele associated with increased birth weight and “q” the alternative allele) and a muscle biopsy was taken from each animal at 300 days of age. Total RNA was isolated and used for NGS library construction and libraries were sequenced on a HiSeq2500 using single-end chemistry. Sequencing yielded 898 million reads (average >30 million reads/sample) that were mapped to the bovine reference genome (Build UMD3.1). Differential gene expression was analyzed using edgeR. Five hundred and seven (507) genes were found to be differentially expressed (FDR P-value < 0.01) in QQ compared to qq animals, including LCORL which was upregulated. Network inferring using weighted gene co-expression network analysis (WGCNA) revealed eleven co-expression gene network modules significantly correlated with genotype. Of these, the LCORL containing module (Blue) showed the highest positive correlation. Gene Ontology enrichment analysis and Ingenuity Pathway Analysis (IPA) revealed an up- and downregulation of lean growth and fat synthesis pathways, respectively, associated with our list of differentially expressed genes; additionally, enrichment and activation of growth and metabolism related-pathways was reported for WGCNA Blue module. Our results suggest that LCORL overexpression may be driving increased cellular metabolism and, consequently, lean growth. Additionally, it suggests that LCORL may be part of a larger complex gene network underlying growth and development, and that the overexpression of this gene may influence the expression pattern of other genes in the same network. Our results provide valuable insights into the molecular mechanisms underlying the phenotypic variation between calves with alternative NCAPG/LCORL genotypes. The characterization of these molecular changes will allow us to better understand the regulation of growth and composition in cattle.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Bioinformatics

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2017

Author dc:creator

• Martins Rodrigues, Fernanda

Contributors dc:contributor

• Beever, Jonathan
• Kukekova, Anna
• Dilger, Anna

• Quantitative trait loci (QTL)
• Quantitative trait nucleotide (QTN)
• Ligand dependent nuclear receptor corepressor‐like (LCORL)
• Non‐SMC condensin I complex subunit G (NCAPG)
• Growth
• Development

Statement dc:rights

• Copyright 2017 Fernanda Martins Rodrigues

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/97639

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/97639