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Molecular technologies have developed rapidly and provide methods to select directly for genes controlling economic traits. The swine genetic linkage map is the most highly developed of all livestock species. Positions on the chromosomes of several genes are known. Some of these genes have been shown to have direct effects on economic traits. Selection lines that differ from the control line by as much as 50% in ovulation rate and litter size exist at Nebraska. This experiment evaluated whether six specific genes that produce important proteins in reproductive processes explained responses in ovulation rate and litter size in two of these lines. The genes studied were follicle stimulating hormone (FSH), prostaglandin endoperoxide-synthase 2 (PTGS2), estrogen receptor (ESR), prolactin receptor (PRLR), retinol binding protein (RBP4), and epidermal growth factor (EGF). Distributions of genotypes for five of the six genes differed among lines. However, line differences in gene frequencies were not greater than what might have occurred due to random genetic drift associated with inbreeding. Furthermore, estimates of the effects of the genes on ovulation rate and litter size were not significant. Therefore, these genes did not have large effects on litter size in this population and did not explain the observed responses to selection. Either other genes with major effects were involved, or there are a large number of genes each with small effects that control expression of the traits. Additional work is being done to determine whether other genes were involved. However, until those genes are identified, swine breeders must rely on traditional breeding methods to improve reproductive traits.