Submitted to: Animal Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 16, 2002
Publication Date: December 1, 2002
Citation: KIM, J.G., NONNEMAN, D.J., VALLET, J.L., ROHRER, G.A., CHRISTENSON, R.K. BRIEF NOTE. LINKAGE MAPPING OF A SINGLE NUCLEOTIDE POLYMORPHISM (SNP) IN THE PORCINE QDPR GENE TO CHROMOSOME 8. ANIMAL GENETICS. 2002. v. 33(6). p. 474. Interpretive Summary: The vitamin, folate, is required for efficient blood cell formation (erythropoiesis) during embryo development in early pregnancy. Therefore, increased folate delivery to the pig embryos may improve erythropoiesis and, thus increase embryo survival and litter size. A recent study showed that intravenous infusion of tetrahydrofolate (active form of folate) did not influence the secreted folate-binding protein. It was reported that folate binding protein, which transports folate to the embryos, increased in the uterus between day 10 and 13 of pregnancy. Mammals do not make tetrahydrofolate but obtain tetrahydrofolate from their diets. Quinoid dihydropteridine reductase (QDPR) is an essential component of the pterin (a part of tetrahydrofolate)-dependent aromatic amino acid hydroxylating systems. In humans, mutations of this gene result in QDPR deficiency. The treatment of QDPR deficiency includes folinic acid therapy. However, QDPR function, cDNA sequence or the chromosomal location of the gene in the chromosome in the pig is not known. To determine whether the QDPR gene influences folate metabolism, embryo survival, and thus litter size, a cDNA clone containing the full coding region of the QDPR (GenBank accession no. AF526879) was isolated from the "Meat Animal Research Center (MARC) 2PIG" expressed sequence tag (EST) library and the QDPR gene was mapped to chromosome 8 position 25.7 cM.
Technical Abstract: Quinoid dihydropteridine reductase (QDPR) catalyzes the NADH-mediated reduction of quinonoid dihydrobiopterin. This enzyme is an essential component of the pterin-dependent aromatic amino acid hydroxylating systems. In humans, mutations of this gene result in QDPR deficiency. Dihydropteridine reductase deficiency presents as atypical phenylketonuria due to insufficient production of biopterin, a cofactor for phenylalanine hydroxylase. The treatment of dihydropteridine reductase deficiency includes folinic acid therapy. A cDNA clone containing the full coding region of the porcine QDPR (GenBank accession no. AF526879) has been isolated from the "Meat Animal Research Center (MARC) 2PIG" expressed sequence tag (EST) primary library. Primers were designed to amplify across the 3' untranslated region (UTR) of the cDNA. The amplified genomic DNA of eight parents (seven F1 sows and one White composite boar) from a subset of the MARC Swine Reference Population were bidirectionally sequenced and evaluated for polymorphisms. An A/G single nucleotide polymorphism was detected. This polymorphism was heterozygous in five of the seven F1 sows and two boars from the MARC Swine Reference Population. An assay was designed to genotype this polymorphism using primer extension with analyte detection on a MALDI-TOF mass spectrometer. This marker generated 153 informative meioses in the MARC Swine Reference Population. The QDPR gene was mapped to chromosome 8 position 25.7 cM, which is the same position as marker PEPS on the current MARC swine chromosome 8 linkage map (http://www.marc.usda.gov/) using CRI-MAP. The most significant two-point linkage detected was with PEPS (LOD = 29.50) at 0 recombination. The QDPR gene in human is located on chromosome 4p15.31, which is syntenic to swine chromosome 8.