Allele-specific expression reveals functional SNPs affecting muscle-related genes in bovine

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Bruscadin, Jennifer Jessica ; Cardoso, Taina Figueiredo ; Diniz, Wellison Jarles da Silva ; Afonso, Juliana ; de Souza, Marcela Maria ; Petrini, Juliana ; Andrade, Bruno Gabriel Nascimento ; da Silva, Vinicius Henrique ; Ferraz, Jose Bento Sterman ; Zerlotini, Adhemar ; Moura, Gerson Barreto ; Coutinho, Luiz Lehmann ; Regitano, Luciana Correia de Almeida

• Tipo de documento: Artigo Científico
• Fonte: BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS; v. 1865, n. 8, p. 14-pg., 2022-10-26.

Resumo

Single nucleotide polymorphisms showing allele-specific expression (ASE SNPs) are useful for cis-regulatory variants discovery. Despite this potential, there are expensive costs involved in genome-level ASE analysis for large sample sizes. If different data resolutions are available, genotype imputation can be used to mitigate this limitation. Aiming to increase the power to detect regulatory variants, we used a large dataset (>4 million) of imputed SNP genotypes and RNA-Seq data from 190 Nelore steers. Differences between major and minor allele expressions in muscle were tested with a Binomial Test. We identified 38,177 ASE SNPs (FDR <= 0.05) within 7304 linkage disequilibrium blocks. After that, we searched for aseQTLs (i.e., neighboring SNPs potentially regulating the ASE SNPs' allelic expression) by comparing the ASE of heterozygous to homozygous sample groups under a Wilcoxon Rank Sum test. We identified 21,543 aseQTLs potentially regulating 430 ASE SNPs (FDR <= 0.05). A total of 3333 cis-eQTLs (being 2098 ASE SNPs and 1075 aseQTLs) were associated with the expression of 758 transcripts (FDR <= 0.05), demonstrating the cis-regulatory effect of these ASE SNPs and aseQTLs. Data integration showed reproducibility with previous studies in bovine ASE and genomic imprinting. Furthermore, we identified 36,756 novel ASE regions due to the imputation approach. Comparisons with epigenetics data from Functional Annotation of Animal Genomes (FAANG) suggest a regulatory potential of the ASE-related SNPs. The affected genes were enriched in metabolic pathways essential for muscle homeostasis. These findings reinforce the potential of using ASE for discovering cis-regulatory SNPs that may affect muscle-related traits. (AU)

• Processo FAPESP: 20/01369-1 - Identificação de variantes com potencial regulador sobre características de qualidade de carne de gado Nelore
• Beneficiário: Jennifer Jessica Bruscadin
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/23638-8 - Bases moleculares da qualidade da carne em bovinos da raça Nelore
• Beneficiário: Luciana Correia de Almeida Regitano
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 12/50533-2 - GIFT: melhoramento genômico de características relacionadas com a fertilização em gado bovino dinamarquês e brasileiro
• Beneficiário: Marcelo Fábio Gouveia Nogueira
• Modalidade de apoio: Auxílio à Pesquisa - Temático