Gene function & annotation

Insertionà¢â‚¬â€œdeletion variation in candidate fitness genes of a local cattle breed

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Abstract

Genetic variation is a key determinant of fitness-related traits in livestock, including growth, fertility, immune response, and adaptability. In cattle, these traits are influenced by both major genes and polygenic effects, collectively referred to as "fitness genes." Previous studies have identified several candidate loci associated with body size, metabolism, immune function, and stress resilience, such as PLAG1, LCORL, NCAPG, PPARGC1A, and BoLA. While single nucleotide polymorphisms (SNPs) are widely studied, insertion-deletion polymorphisms (indels) represent an additional source of genetic variation capable of altering gene function through frameshifts, splice site disruption, or regulatory modifications.In this study, whole-genome sequencing was performed on 19 Alpine Grey cattle to investigate indels within 23 candidate genes related to growth, metabolism, immunity, and reproduction (ANGPT1, PPARGC1A, GBE1, SOD1, HSPA13, OXCT1, PLAG1, LCORL, NCAPG, HMGA2, XKR4, FGF6, SOD2, TGFBR1, CSPP1, ANXA1, PCSK5, JMJD1C, NOD1, ITGB2, IRAK3, MZB1, and BoLA). High-confidence variants were identified using a standardized bioinformatic pipeline including FastQC, fastp, BWA-MEM, samtools, and GATK HaplotypeCaller, followed by functional annotation with SnpEff. Indels were extracted, and genotype counts were computed for each individual.Whole-genome sequencing yielded 19,074,015 variants, including 1,521,987 insertions and 1,516,568 deletions. Among these, 4,441 high-impact indels were identified, predominantly frameshift variants, along with splice donor/acceptor, stop-gained, and stop-lost indels. Within the candidate genes, allelic variation was observed in LCORL, PCSK5, and BoLA. LCORL harbored one high-impact indel present in 18 individuals, PCSK5 contained a single indel in one individual, and BoLA displayed multiple high-impact indels across chromosome 23, indicating substantial allelic diversity.To further characterize the functional impact of these indels, the Variant Effect Predictor (VEP, version 115.1, ARS-UCD2.0 reference genome) was employed. Sixteen variants were successfully annotated, with 43.8% classified as novel and 56.2% as existing. No pathogenic variants were detected. Most novel allelic variants were of uncertain significance, although some showed predicted functional effects. Notably, a variant in PCSK5 was predicted to be involved in several biological processes related to embryonic and organ development, protein processing, and proteolytic activity, highlighting its potential biological relevance.These findings highlight the potential of the value of indel analysis for identifying functionally relevant variation in fitness-associated genes. The detected high-impact indels, supported by functional annotation, provide a foundation for future studies aimed at elucidating gene function and for their potential integration into genomic selection programs to enhance productivity, health, and adaptability in cattle.

Keywords: 2026

How to Cite:

Oian, A., Mancin, E., Gomez Proto, G., Rulli, E., Sartori, C. & Mantovani, R., (2026) “Insertionà¢â‚¬â€œdeletion variation in candidate fitness genes of a local cattle breed”, World Congress on Genetics Applied to Livestock Production Digital Archive 2026(1): 2283153. doi: https://doi.org/10.31274/wcgalp.23489

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