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Previous studies showed that the NLR family pyrin domain-containing 5 (NLRP5) and NLRP9 genes are two important reproductive genes; however, their effects on sheep litter size are unknown. Therefore, in this study, we first genotyped seven sheep breeds via the MassARRAY ® SNP system at the loci g.60495375A &gt; G, g.60495363G &gt; A, and g.60499690C &gt; A in NLRP5 , and g.59030623T &gt; C and g.59043397A &gt; C in NLRP9 . Our results revealed that each locus in most sheep breeds contained three genotypes. Then, we conducted population genetic analysis of single nucleotide polymorphisms in NLRP5 and NLRP9 , and we found that the polymorphism information content value in all sheep breeds ranged from 0 to 0.36, and most sheep breeds were under Hardy-Weinberg equilibrium ( p &gt; 0.05). Furthermore, association analysis in Small Tail Han sheep indicated that two loci, g.60495363G &gt; A in NLRP5 and g.59030623T &gt; C in NLRP9 , were highly associated with litter size. The mutation in g.60495363G &gt; A may decrease interactions of NLRP5 with proteins, such as GDF9, whereas the mutation in g.59030623T &gt; C may enhance the combining capacity of NLRP9 with these proteins; consequently, these mutations may influence the ovulation rate and even litter size. The findings of our study provide valuable genetic markers that can be used to improve the breeding of sheep and even other mammals.

Mutations in NLRP5 and NLRP9 Are Associated with Litter Size in Small Tail Han Sheep