Molecular Insights into the Genetic Regulation of Calving Interval in Tropical Cattle Breeds

Calving interval (CI) is a multifactorial reproductive trait regulated by both genetic and environmental influences. Although its heritability is relatively low, the genetic basis of CI is highly relevant as it reflects the inherent reproductive efficiency of cattle. The underlying genetic mechanisms affecting CI, however, remain to be clarified. In this study, a whole-genome comparative analysis of five Bos indicus breeds from the Indian subcontinent—Kangayam, Tharparkar, Sahiwal, Red Sindhi, and Hariana, was performed. The NCBI public database was used in this study. The Mark Duplicates tool of Picard tools was used to remove potential PCR duplicates from the aligned reads, and then the uniquely mapped reads were used for the variant calling step. The free bayes output was filtered to include high-quality variants in the candidate genes, that is, quality (QUAL > 1). Furthermore, the identified SNP/InDels were classified as high, moderate, low, and modifier using the SnpEff tool. Across these breeds, 17,252 genes carrying single-nucleotide polymorphisms (SNPs) or InDels predicted to have high or moderate impact on protein function were identified. From these, 57 potential candidate genes associated with CI were detected, including LTF, SELP, GC, LENG8, LEPR, GHR, GH1, RPS9, TLR4, GNRHR, ARHGAP29, SEC24D, METTL14, SLC36A2, SLC36A3, APBA3, TCF12, and ZFR2. Functional annotation revealed enrichment of biological processes such as cellular response to hormonal stimuli, regulation of insulin-like growth factor receptor signalling, glucose metabolism, peptide and lipid responses, and ovulation cycle processes. Pathway enrichment highlighted neuroactive ligand-receptor interactions along with growth hormone and prolactin receptor signalling pathways. Network analysis further identified ESR1, IGF1, LEP, MSTN, TNF, FGF2, TLR4, and LTF as central hub genes with potential regulatory influence on CI in indicine cattle. Overall, this study uncovers genomic variants and key molecular pathways that provide novel insights into the genetic regulation of CI in indigenous Bos indicus breeds adapted to tropical conditions. The discovered genetic variants hold potential applications in the development of customised SNP genotyping chips, as well as in marker-assisted and genomic selection programs for cattle breeding in the future.