Abstract
The alpha-1,3-galactosyltransferase 1 enzyme (GGTA1) produces the α-Gal epitopes, responsible for pig-to-human hyperacute xenograft rejection. Recently, efforts have been directed at inactivating the porcineGGTA1 gene in order to reduce hyperacute rejection. As very little is known about the genetic variability of this key gene among pig breeds, we investigated the variation in its nucleotide sequence, by amplification of the entire coding region with the use of polymerase chain reaction followed by DNA sequencing. Eight commercial pig populations were analysed and 17 single nucleotide polymorphisms (SNPs) were detected: 11 in intronic regions and 6 in the 3′ untranslated region (UTR). No SNPs change the encoded protein; however, 8 of these SNPs may alter the transcriptional regulation and pre-mRNA splicing ofGGTA1.
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References
Calne RY, 1970. Organ transplantation between widely disparate species. Transplant Proc 2: 550–556.
Cartegni L, Chew SL, Krainer AR, 2002. Listening to silence and understanding nonsense: exonic mutations that affect splicing. Nat Rev Genet 3: 285–298.
Cooper DKC, Good AH, Koren E, Oriol R, Malcolm AJ, Ippolito RM, et al. 1993. Identification of alpha-galactosyl and other carbohydrate epitopes that are bound by human anti-pig antibodies: relevance to discordant xenografting in man. Transpl Immunol 1: 198–205.
Dai Y, Vaught TD, Boone J, Chen SH, Phelps CJ, Ball S, et al. 2002. Targeted disruption of the α-l,3-galactosyltransferase gene in cloned pigs. Nat Biotechnol 20: 251–255.
Galili U, Shohet SB, Kobrin E, Stults CL, Macher BA, 1998. Man, apes, and Old World monkeys differ from other mammals in the expression of alpha-galactosyl epitopes on nucleated cells. J Biol Chem 263: 17755–17762.
Joziasse DH, Shaper JH, van den Eijnden DH, van Tunen AJ, Shaper NL, 1989. Bovine alpha 1-3-galactosyltransferase: isolation and characterization of a cDNA clone. Identification of homologous sequences in human genomic DNA. J Biol Chem 264: 14290–14297.
Joziasse DH, Shaper NL, Kim D, van den Eijnden DH, Shaper JH, 1992. Murine alpha 1,3-galactosyltransferase: A single gene locus specifies four isoforms of the enzyme by alternative splicing. J Biol Chem 267: 5534–5541.
Katayama A, Ogawa H, Kadomatsu K, Kurosawa N, Kobayashi T, Kaneda N, et al. 1998. Porcine α-l,3-galactosyltransferase: full length cDNA cloning, genomic organization, and analysis of splicing variants. Glycoconj J 15: 583–589.
Koike C, Friday RP, Nakashima I, Luppi P, Fung JJ, Rao AS, et al. 2000. Isolation of the regulatory regions and genomic organization of the porcine alpha 1,3-galactosyltransferase gene. Transplantation 70: 1275–1283.
Lai L, Kolber-Simonds D, Park KW, Cheong HT, Greenstein JL, Im GS, et al. 2002. Production of α-l,3-galactosyltransferase knockout pigs by nuclear transfer cloning. Science 295: 1089–1092.
Larsen RD, Rajan VP, Ruff MM, Kukowska-Latallo J, Cummings RD, Lowe JB, 1989. Isolation of a cDNA encoding a murine UDPgalactose: beta-D-galactosyl-1,4-N-acetyl-D-glucosaminide alpha-1, 3-galactosyltransferase: expression cloning by gene transfer. Proc Natl Acad Sci USA 86: 8227–8231.
Mercier D, Charreau B, Wierinckx A, Keijser R, Adriaensens L, van den Berg R, Joziasse DH, 2002. Regulation of alpha 1,3-galactosyltransferase expression in pig endothelial cells. Implications for xenotransplantation. Eur J Biochem 269: 1464–1473.
Oriol R, Barthod F, Bergemer AM, Ye Y, Koren E, Cooper DKC, 1994. Monomorphic and polymorphic carbohydrate antigens on pig tissues: implications for organ xenotransplantation in the pig-to-human model. Transpl Int 7: 405–413.
Phelps CJ, Koike C, Vaught TD, Boone J, Wells KD, Chen SH, et al. 2003. Production of α-l,3-galactosyltransferase-deficientpigs. Science 299: 411–414.
Sachs DH, 1994. The pig as a xenograft donor. Pathol Biol 42: 217–219.
Sandrin MS, Dabkowski PL, Henning MM, Mouhtouris E, McKenzie IFC, 1994. Characterization of cDNA clones for pig α(l,3)galactosyl transferase: the enzyme generating the Gala(1,3)Gal epitope. Xenotransplantation 1: 81–88.
Vanhove B, Goret F, Soulillou JP, Pourcel C, 1997. Porcine α-1,3-galactosyltransferase: tissue-specific and regulated expression of splicing isoforms. Biochim Biophys Acta 1356: 1–11.
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Day, A., Rocha, D. Allelic variation of the porcine α-1,3-galactosyltransferase 1 (GGTA1) gene. J Appl Genet 49, 75–79 (2008). https://doi.org/10.1007/BF03195251
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DOI: https://doi.org/10.1007/BF03195251