Abstract
Improved reproductive efficiency could lead to economic benefits for the beef industry, once the intensive selection pressure has led to a decreased fertility. However, several factors limit our understanding of fertility traits, including genetic differences between populations and statistical limitations. In the present study, the RNA-sequencing data from uterine samples of high-fertile (HF) and sub-fertile (SF) animals was integrated using co-expression network meta-analysis, weighted gene correlation network analysis, identification of upstream regulators, variant calling, and network topology approaches. Using this pipeline, top hub-genes harboring fixed variants (HF × SF) were identified in differentially co-expressed gene modules (DcoExp). The functional prioritization analysis identified the genes with highest potential to be key-regulators of the DcoExp modules between HF and SF animals. Consequently, 32 functional candidate genes (10 upstream regulators and 22 top hub-genes of DcoExp modules) were identified. These genes were associated with the regulation of relevant biological processes for fertility, such as embryonic development, germ cell proliferation, and ovarian hormone regulation. Additionally, 100 candidate variants (single nucleotide polymorphisms (SNPs) and insertions and deletions (INDELs)) were identified within those genes. In the long-term, the results obtained here may help to reduce the frequency of subfertility in beef herds, reducing the associated economic losses caused by this condition.
Highlights
Intensive selection pressure has led to a decrease in fertility efficiency in both beef and dairy cattle populations [1,2]
In the long-term, the results obtained here may help to reduce the frequency of subfertility in beef herds, reducing the associated economic losses caused by this condition
0.4 (p-value < 1.7 × 10−191) for the ranked connectivity between the HF and SF samples. These results indicate that both datasets are suitable to be analyzed together for the identification of co-expressed gene networks owing to the strong correlation observed
Summary
Intensive selection pressure has led to a decrease in fertility efficiency in both beef and dairy cattle populations [1,2]. Genetic mechanisms such as pleiotropy, genetic hitchhiking, and epistasis can be the cause of the genetic correlations, and consequent undesirable effects, observed between production and fertility traits [3,4,5,6,7]. Sub-fertile animals can generate progeny, maintaining the causal alleles for this phenotype in the population [15]. The causal alleles for the infertile phenotype tend to reduce its allelic frequency naturally across time owing to the
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