# Association Analysis of BRCA1, PPAP2B, and KCNN3 Gene Polymorphisms With Litter Size in Sheep

## TL;DR

This study explores how genetic variations in three genes may affect the number of offspring in sheep, offering insights for improving breeding efficiency.

## Contribution

The study identifies BRCA1, PPAP2B, and KCNN3 gene polymorphisms as potential genetic markers for sheep litter size, with breed-specific associations.

## Key findings

- BRCA1 polymorphisms showed significant differences in genotype and allele frequencies between high- and low-prolificacy sheep breeds.
- The PPAP2B GG genotype was more frequent in Small-Tailed Han sheep with higher fecundity.
- KCNN3 polymorphisms exhibited breed-specific associations but deviated from Hardy-Weinberg equilibrium in some breeds.

## Abstract

Reproductive efficiency is a key economic trait in sheep production, with litter size being a major determinant of productivity. Genetic polymorphisms in candidate genes such as BRCA1, PPAP2B, and KCNN3 may influence fecundity, but their association with sheep prolificacy remains to be fully elucidated. Identifying genetic markers linked to high litter size could enhance breeding strategies for improved reproductive performance.

This study aimed to (1) investigate the relationship between BRCA1, PPAP2B, and KCNN3 gene polymorphisms and sheep litter size and (2) identify potential genetic markers for high fecundity in sheep.

Whole‐genome resequencing combined with Sequenom MassARRAY SNP genotyping was used to analyze five polymorphic loci in BRCA1, PPAP2B, and KCNN3 across five sheep breeds, including high‐prolificacy breeds (Small‐Tailed Han sheep, Hu Sheep, and Cele Black Sheep) and low‐prolificacy breeds (Sunite sheep and Bamei mutton sheep). Small‐Tailed Han sheep were selected for association analysis with litter size. Chi‐square tests assessed Hardy–Weinberg equilibrium (HWE), and association studies evaluated genotype effects on reproductive traits.

BRCA1 gene polymorphisms (g.42581575 T > C, g.42560830 A > T, g.42548851 C > T) exhibited significant differences (p < 0.01) in genotype and allele frequencies between high‐ and low‐prolificacy breeds. All three loci were in HWE (p > 0.05) except in Hu sheep. The KCNN3 g.103522805 C > A locus also showed significant frequency differences (p < 0.01) between breeds but deviated from HWE in Bamei mutton sheep (p < 0.05).Only the PPAP2B g.77092130 G> A locus demonstrated a significant association (p > 0.05) with litter size in Small‐Tailed Han sheep, where the GG genotype was more frequent than the AA genotype in the second parity.

This study identified BRCA1, PPAP2B, and KCNN3 as potential genetic markers influencing sheep litter size. The BRCA1 and KCNN3 polymorphisms showed strong breed‐specific associations, while the PPAP2B GG genotype may favor higher fecundity in Small‐Tailed Han sheep. These findings provide valuable insights for marker‐assisted selection in sheep breeding programs aimed at improving reproductive efficiency. Further functional studies are needed to validate the biological mechanisms underlying these genetic associations.