biostudies-literatureYang Sthe State Key Laboratory for Reproductive Regulation and Breeding of Grassland Livestockthe Major Science and Technology Projects of Inner Mongoliathe Central Guidance for Local Scientific and Technological Development Plan of Chinathe High Level Overseas Talents Project from the Ministry of Human Resources and Social Security of Chinathe Xilingol Science & Technology Planthe Major Demonstration Projects for Technological Innovation of Inner Mongolia868https://www.ebi.ac.uk/biostudies/studies/S-EPMC12474046biostudies-literatureUnknown12(9)Increasing the litter size in sheep is a primary objective in breeding programs, driving sustained interest in identifying candidate functional genes and molecular markers associated with fecundity. The known FecD mutation in the <i>LEPR</i> gene has been shown to regulate reproductive traits by influencing the ovulation rate of Davisdale sheep. However, the relationship between single-nucleotide polymorphisms (SNPs) in the <i>LEPR</i> and litter size remains unknown in Gobi short tail sheep and Sonid sheep. In this research, we found one novel variant and thirteen known variants through direct sequencing in Sonid sheep and Gobi short tail sheep and performed an association study in a large-scale population. The association analysis identified two SNPs (c.240C>T (rs159694506) and c.279C>T Veterinary sciencesEffects of Novel Mutations in the &lt;i&gt;LEPR&lt;/i&gt; Gene on Litter Size in Gobi Short Tail Sheep and Sonid Sheep.PMC12474046No. 2021ZZ0204 and 2025SKYPT0081No. 2025ZY0051No. 2021ZD0046No. 2025SZDSF0012No. GD202210[2018] No. 190Tong BBaoying TLi CCao GAn LDa LZhang MYang SDong PfalseEffects of Novel Mutations in the &lt;i&gt;LEPR&lt;/i&gt; Gene on Litter Size in Gobi Short Tail Sheep and Sonid Sheep.Increasing the litter size in sheep is a primary objective in breeding programs, driving sustained interest in identifying candidate functional genes and molecular markers associated with fecundity. The known FecD mutation in the <i>LEPR</i> gene has been shown to regulate reproductive traits by influencing the ovulation rate of Davisdale sheep. However, the relationship between single-nucleotide polymorphisms (SNPs) in the <i>LEPR</i> and litter size remains unknown in Gobi short tail sheep and Sonid sheep. In this research, we found one novel variant and thirteen known variants through direct sequencing in Sonid sheep and Gobi short tail sheep and performed an association study in a large-scale population. The association analysis identified two SNPs (c.240C>T (rs159694506) and c.279C>T 2025-01-01T00:00:00Z2025 Sep2026-05-02T03:18:27.45Z2026-05-02T03:11:47.779ZS-EPMC124740464101279210.3390/vetsci12090868