Single nucleotide polymorphisms (SNPs) located in transcript sequences showing allele-specific expression (ASE SNPs) were previously identified in the Longissimus thoracis muscle of a Nelore (Bos indicus) population consisting of 190 steers. Given that the allele-specific expression pattern may result from cis-regulatory SNPs, called allele-specific expression quantitative trait loci (aseQTLs), in this study, we searched for aseQTLs in a window of 1 Mb upstream and downstream from each ASE SNP. After this initial analysis, aiming to investigate variants with a potential regulatory role, we further screened our aseQTL data for sequence similarity with transcription factor binding sites and microRNA (miRNA) binding sites. These aseQTLs were overlapped with methylation data from reduced representation bisulfite sequencing (RRBS) obtained from 12 animals of the same population. We identified 1134 aseQTLs associated with 126 different ASE SNPs. For 215 aseQTLs, one allele potentially affected the affinity of a muscle-expressed transcription factor to its binding site. 162 aseQTLs were predicted to affect 149 miRNA binding sites, from which 114 miRNAs were expressed in muscle. Also, 16 aseQTLs were methylated in our population. Integration of aseQTL with GWAS data revealed enrichment for traits such as meat tenderness, ribeye area, and intramuscular fat . To our knowledge, this is the first report of aseQTLs identification in bovine muscle. Our findings indicate that variouscis-regulatory and epigenetic mechanisms can affect multiple variants to modulate the allelic expression.
Fig: SNPs and aseQTLs distribution through the bovine chromosomes, overlap with previous QTL studies and predicted aseQTL regulatory mechanisms (TFBS, miRNA binding site, or methylated site). ASE SNPs: SNPs in transcripts with allele-specific expression, only the ASE SNPs with significant aseQTLs are displayed. aseQTL: identified allele-specific quantitative trait loci (aseQTLs). Overlapped: aseQTLs that overlaps with previous GWAS data made from our group. TFBS: aseQTLs that possibly enable the TF binding in only one allele. miRNA-BS: aseQTLs that potentially modify miRNA binding sites in only one allele. Methylated: methylated aseQTLs. The color intensity increases with increasing SNPs density in the plot scale (1 bp windows). This figure was made using the software CircosVCF.
Some of the potential regulatory variants described here were associated with the expression pattern of genes related to interesting phenotypes for livestock. Thus, these variants might be useful for the comprehension of the genetic control of these phenotypes.
Bruscadin, J.J., de Souza, M.M., de Oliveira, K.S. et al. Muscle allele-specific expression QTLs may affect meat quality traits in Bos indicus.Sci Rep 11, 7321 (2021). https://doi.org/10.1038/s41598-021-86782-2