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Interferon-induced transmembrane protein 3 (IFITM3), a crucial effector of the host’s innate immune system, prohibits an extensive range of viruses. Previous studies have reported that single nucleotide polymorphisms (SNPs) of the  IFITM3  gene are associated with the expression level and length of the IFITM3 protein and can impact susceptibility to infectious viruses and the severity of infection with these viruses. However, there have been no studies on polymorphisms of the bovine  IFITM3  gene. In the present study, we finely mapped the bovine  IFITM3  gene and annotated the identified polymorphisms. We investigated polymorphisms of the bovine  IFITM3  gene in 108 Hanwoo and 113 Holstein cattle using direct sequencing and analyzed genotype, allele, and haplotype frequencies and linkage disequilibrium (LD) between the  IFITM3  genes of the two cattle breeds. In addition, we analyzed transcription factor-binding sites and transcriptional capacity using PROMO and luciferase assays, respectively. Furthermore, we analyzed the effect of a nonsynonymous SNP of the  IFITM3  gene using PolyPhen-2, PANTHER, and PROVEAN. We identified 23 polymorphisms in the bovine  IFITM3  gene and found significantly different genotype, allele, and haplotype frequency distributions and LD scores between polymorphisms of the bovine  IFITM3  gene in Hanwoo and Holstein cattle. In addition, the ability to bind the transcription factor Nkx2-1 and transcriptional capacities were significantly different depending on the c.-193T > C allele. Furthermore, nonsynonymous SNP (F121L) was predicted to be benign. To the best of our knowledge, this is the first genetic study of bovine  IFITM3  polymorphisms.

Regulatory Single Nucleotide Polymorphism of the Bovine IFITM3 Gene Induces Differential Transcriptional Capacities of Hanwoo and Holstein Cattle