PSV-8 Investigation of a haplotype and eQTL analysis of the LCORL-NCAPG locus associated with increased lean growth in beef cattle

Abstract Numerous studies have shown genetic variation at the LCORL-NCAPG locus is strongly associated with growth traits in beef cattle. However, a causative molecular variant has yet to be identified. To define all possible candidate variants, Charolais-sired calves (n = 34) were whole genome sequenced including 17 homozygous for a long-range haplotype associated with increased growth (QQ), and 17 homozygous for potential ancestral haplotypes for this region (qq). The Q haplotype was refined to an 814-kb region between chr6:37,199,897-38,014,080 and contained 218 variants not found in qq individuals. These variants include an insertion in an intron of NCAPG, a previously documented mutation in NCAPG (rs109570900), two coding sequence mutations in LCORL (rs109696064 and rs384548488), and 15 variants located within ATAC peaks that were predicted to affect transcription factor binding. Notably, rs384548488 is a frameshift variant likely resulting in loss of function for long isoforms of LCORL. To test the association of the coding sequence variants of LCORL with phenotype, 405 cattle from five populations were genotyped. The two variants were in complete linkage disequilibrium. Statistical analysis of the three populations that contained QQ animals revealed significant (P < 0.05) associations with genotype and birth weight, body weight, carcass weight, hip height, and average daily gain. Additionally, an RNAseq analysis was performed using 22 of the Charolais-sired calves. This, in conjunction with the WGS data, was used to run an eQTL analysis, which revealed 256 genes whose expression were impacted by eQTL in the region (FDR < 0.05). These findings affirm the link between this locus and growth in beef cattle and describe DNA variants that define the haplotype. However, further studies will be required to define the true causative mutation.