# Novel Silent Mutations in the HIRA Gene Associated with Litter Size in Sonid Sheep

## TL;DR

This study found new mutations in the HIRA gene linked to litter size in Sonid sheep, offering potential genetic markers for improving sheep breeding.

## Contribution

The study identifies 15 novel HIRA gene mutations in Sonid sheep, some of which are associated with litter size and predicted to affect protein structure.

## Key findings

- Three HIRA gene mutations (c.1521C>G, c.1572C>T, c.1578G>A) are significantly associated with litter size in Sonid sheep.
- Two mutations (c.1273G>A and c.1735A>G) are predicted to alter the protein structure of HIRA.
- The mutations may enhance mRNA stability by lowering the minimum free energy of the secondary structure.

## Abstract

This study investigated the association between genetic variants of the HIRA gene and litter size in Sonid sheep. Through analysis, we identified fifteen novel mutations in the HIRA gene. Among these, the c.1521C>G, c.1572C>T, and c.1578G>A variants were associated with litter size, while c.1273G>A and c.1735A>G were predicted to alter protein structure. These variants could serve as valuable genetic markers for improving prolificacy in sheep breeding and highlight new variants for further functional research on the HIRA gene.

Improving ovine reproductive efficiency is an important breeding goal that could substantially enhance economic viability in the sheep industry. The histone cell cycle regulator (HIRA) gene has been functionally validated as a reproductive regulator in model organisms such as Drosophila and murine species; however, research on the effects of HIRA on the prolificacy in sheep remains scarce. Thus, this study aimed to investigate the association between genetic variants of HIRA and litter size in sheep. In brief, we identified 15 novel exonic mutations in the Sonid sheep breed via direct sequencing. Notably, a linkage disequilibrium including the c.1521C>G, c.1572C>T, and c.1578G>A mutations on exon 14 of HIRA exhibited a significant association with litter size in Sonid sheep (p < 0.01). Meanwhile, it was predicted that mutations play a major role in enhancing the stability of the mRNA secondary structure by lowering the minimum free energy, and mutations were also thought to change the mRNA secondary structure of ovine HIRA. Therefore, these findings may provide potentially useful molecular markers for optimizing reproductive performance in Sonid sheep.