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Title: ALLELIC VARIATION IN THE SECRETED FOLATE BINDING PROTEIN GENE IS ASSOCIATED WITH UTERINE CAPACITY IN SWINE

Author
item Vallet, Jeff
item Freking, Bradley - Brad
item Leymaster, Kreg
item Christenson, Ronald

Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/7/2005
Publication Date: 8/20/2005
Citation: Vallet, J.L., Freking, B.A., Leymaster, K.A., Christenson, R. 2005. Allelic variation in the secreted folate binding protein gene is associated with uterine capacity in swine. Journal of Animal Science. 83(8):1860-1867.

Interpretive Summary: Litter size of pigs is a major determinant of the efficiency of swine production. Folate is a vitamin that is important for protein and DNA synthesis in cells, and is especially important for red blood cell development and for the appropriate development of the fetus during pregnancy. Folate is delivered to the developing swine fetus bound to an intrauterine protein called secreted folate binding protein. We determined the association between DNA sequence variation in the secreted folate binding protein gene and reproductive traits including the number of eggs shed per reproductive cycle, the percentage of embryos that die before day 11 of pregnancy, and uterine capacity (the number of fetuses that can be maintained by the uterus). The number of eggs shed per reproductive cycle, the percentage of those eggs fertilized by sperm, the percentage of embryos that die during early pregnancy, and the ability of the uterus to carry pig fetuses to term are all components of overall litter size in pigs. DNA sequence variation in the sFBP gene was associated with differences in uterine capacity, the number of eggs shed per reproductive cycle and the percentage of embryos that die before day 11 of pregnancy. Because sequence variation in the sFBP gene affected more than one factor ultimately influencing litter size, the overall effect of variation in the sequence of the sFBP gene on litter size was negligible, making these markers unlikely to be useful in altering litter size in pigs. However, the results indicate that secreted folate binding protein plays important roles in the different components of litter size, and further research is needed to determine the role of secreted folate binding protein in the component traits of litter size in pigs.

Technical Abstract: Previous comparisons between the cDNA and gene sequences for secreted folate binding protein (sFBP) indicated two polymorphisms, a 12 bp insertion/deletion (in/del) polymorphism in exon 1, corresponding to a part of the 5' untranslated region, and a single nucleotide polymorphism (SNP) that altered (Ser-Arg) the protein amino acid sequence in exon 5. Experiments were undertaken to determine the effects of these polymorphisms on reproductive traits. The Ser-Arg SNP appeared to be present only in Meishans. Thus, the effect of this SNP on reproductive traits in three groups of Meishan-White European breed crossbred gilts was examined. The gilts for all three groups were unilaterally hysterectomized-ovariectomized (UHO) at 100 d of age. Group 1 gilts (n = 77) were mated at estrus and slaughtered at d 105 of pregnancy. At slaughter, a blood sample was collected from each fetus to determine fetal hematocrit. The number of CL and fetuses and the weights of each fetus and associated placenta were recorded. Group 2 gilts (n = 46) were mated and laparotomized on d 11 of pregnancy. The remaining uterine horn was flushed with 20 ml saline and flushings were measured for total sFBP. Gilts were allowed a full estrous cycle to recover from surgery, mated again at estrus, slaughtered at 105 d of gestation, and the data as described for group 1 was collected. Groups 1 and 2 gilts were genotyped for the Ser-Arg SNP. In group 3, Gilts (n = 70) and boars (n = 30) were genotyped for the Ser-Arg SNP before mating, and like genotypes were mated. Gilts were then treated as described for group 2. The association between the second sFBP polymorphism (12 bp in/del) and reproductive traits was examined in 407 white crossbred UHO gilts from a randomly selected control line, a line selected for ovulation rate (OR) and a line selected for uterine capacity (UC). Gilts were mated and slaughtered at 105 d of age, and the number of CL, the number of live fetuses, the weight of each fetus and placenta, and each fetal hematocrit was recorded. In addition, the 12 bp in/del was evaluated in a separate set of 131 intact gilts from the OR selected line. Gilts were mated at approximately 250 d of age and farrowed. At farrowing, the numbers of fully-formed and live piglets were recorded. The sFBP Ser-Arg SNP was associated (P < 0.05) with differences in the number of embryos present on d 11 of pregnancy, and with differences in uterine capacity. The sFBP in/del polymorphism was associated with uterine capacity (P < 0.01) and the number of corpora lutea (P < 0.05) in UHO gilts. However, litter size was not associated with the sFBP in/del polymorphism in intact gilts from the OR line. These results indicate that genetic variation in the sFBP gene is associated with uterine capacity in gilts. These markers could be exploited to increase litter size in swine, provided the negative effects of sFBP gene polymorphisms on ovulation rate, fertilization rate and/or embryo survival are overcome.