Journal of Applied Genetics

, Volume 49, Issue 1, pp 75–79 | Cite as

Allelic variation of the porcine α-1,3-galactosyltransferase 1 (GGTA1) gene

Original Article


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.


alternative splicing GGTA1 pig breeds porcine single nucleotide polymorphism transcription factor binding site 


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  1. Calne RY, 1970. Organ transplantation between widely disparate species. Transplant Proc 2: 550–556.PubMedGoogle Scholar
  2. Cartegni L, Chew SL, Krainer AR, 2002. Listening to silence and understanding nonsense: exonic mutations that affect splicing. Nat Rev Genet 3: 285–298.CrossRefPubMedGoogle Scholar
  3. 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.CrossRefPubMedGoogle Scholar
  4. 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.CrossRefPubMedGoogle Scholar
  5. 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.Google Scholar
  6. 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.PubMedGoogle Scholar
  7. 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.PubMedGoogle Scholar
  8. 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.CrossRefPubMedGoogle Scholar
  9. 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.CrossRefPubMedGoogle Scholar
  10. 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.CrossRefPubMedGoogle Scholar
  11. 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.CrossRefPubMedGoogle Scholar
  12. 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.CrossRefPubMedGoogle Scholar
  13. 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.CrossRefPubMedGoogle Scholar
  14. 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.CrossRefPubMedGoogle Scholar
  15. Sachs DH, 1994. The pig as a xenograft donor. Pathol Biol 42: 217–219.PubMedGoogle Scholar
  16. 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.CrossRefGoogle Scholar
  17. 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.CrossRefPubMedGoogle Scholar

Copyright information

© Institute of Plant Genetics, Polish Academy of Sciences, Poznan 2008

Authors and Affiliations

  1. 1.Genus plc, Genus Cambridge Research LaboratoryUniversity of Cambridge, Department of PathologyCambridgeUK
  2. 2.UMR1061INRA — Université de Limoges, Faculté des SciencesLimogesFrance

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