OMIA 001089-9823 : Blood group system ABO in Sus scrofa

See the equivalent entry at NCBI

In other species: olive baboon , Japanese macaque , chimpanzee , Rhesus monkey , crab-eating macaque , agile gibbon , common gibbon , siamang

Possible human homologue (MIM number): 110300

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key mutation known: yes

Year key mutation first reported: 2001

Cross-species summary: Each blood group system consists of a set of blood types, each of which corresponds to a particular antigen (usually a glycoprotein) on the surface of red blood cells. The different types within a system are the result of the action of different alleles at a locus that usually encodes an enzyme that catalyses the creation of the feature of the glycoprotein unique to that type, e.g. the presence of a particular sugar at the end of a short chain of sugars. The ABO blood group system arises from two alleles at a locus that encodes a glycosyltransferase: the A allele encodes alpha 1-3-N-acetylgalactosaminyltransferase; and the B allele encodes alpha 1-3-galactosyltransferase. The B allele transferase catalyses the addition of galactose to a chain of four sugars attached to a protein known as H antigen. The A allele ltransferase catalyses the addition of a derivative of galactose called N-acetylgalactosamine to the same short chain of sugars. The third allele at this locus (the O allele) results in no sugar being added to the chain.

Species-specific description: Pigs have just two alleles at this locus, namely A and O (Yamamoto and Yamamoto, 2001). The A antigen is known as the major xenotransplantation antigen or major xenoantigen.

Variants of this trait have been created artificially: Genetically-modifed organism; GMO.

History: Sprague (1958) was among the first to suggest that pigs may have an ABO-like blood group system (on the basis of the reaction of pig red blood cells to typing sera from cattle). His observations were confirmed by Andresen (1962) and Saison and Imgram (1962).

Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), Yamamoto and Yamamoto (2001) showed that the A allele corresponds to a functional GGTA1 gene, whereas the O allele includes a major deletion of this gene.

Nguyen et al. (2011) provided more detail on this deletion: "the 0 allele has a large deletion between exon 7 of the A0 blood group gene and the neighbouring SURF6".

Using transcription activator-like effector nucleases (TALENs) to generate GGTA1 knockout fibroblast cell lines, which were then used in somatic cell nuclear transfer, Xin et al. (2013) generated pigs with no effective GGTA1 genes, which "can provide a new organ source for xenotransplantation research".

Kan et al. (2016) achieved a similar result with the same technology; Petersen et al. (2016) achieved a similar results with CRISPR/Cas9 technology.

Clinical features: The clinical importance of porcine AO antigens relates to the use of pig tissue and organs in transplantation to humans (xenotransplantation): the major cell-surface antigen causing rejection in porcine-human xenotransplantation is the A antigen produced by the enzyme encoded by this locus, i.e. by the enzyme alpha1-3 N-acetyl-D-galactosaminyltransferase (known as "gal transferase [GT]"), encoded by GGTA1. Consequently, as soon as gene knockout and animal cloning technology became available (i.e. in vitro gene knockout, followed by somatic cell nuclear transfer to produce cloned animals), clones of gal-transferase knockout (GTKO) pigs were produced for use as donors in xenotransplantation. The first GTKO pigs were produced by Lai et al. (2002).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
GGTA1 glycoprotein, alpha-galactosyltransferase 1 Sus scrofa 1 NC_010443.5 (261587968..261511304) GGTA1 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective.

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Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Blood group system ABO GGTA1 O deletion, gross (>20) "the 0 allele has a large deletion between exon 7 of the A0 blood group gene and the neighbouring SURF6". 2011 21554350

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2017 Chuang, C.K., Chen, C.H., Huang, C.L., Su, Y.H., Peng, S.H., Lin, T.Y., Tai, H.C., Yang, T.S., Tu, C.F. :
Generation of GGTA1 Mutant Pigs by Direct Pronuclear Microinjection of CRISPR/Cas9 Plasmid Vectors. Anim Biotechnol 28:174-181, 2017. Pubmed reference: 27834588. DOI: 10.1080/10495398.2016.1246453.
2016 Cheng, W., Zhao, H., Yu, H., Xin, J., Wang, J., Zeng, L., Yuan, Z., Qing, Y., Li, H., Jia, B., Yang, C., Shen, Y., Zhao, L., Pan, W., Zhao, H.Y., Wang, W., Wei, H.J. :
Efficient generation of GGTA1-null Diannan miniature pigs using TALENs combined with somatic cell nuclear transfer. Reprod Biol Endocrinol 14:77, 2016. Pubmed reference: 27821126. DOI: 10.1186/s12958-016-0212-7.
Choi, K., Shim, J., Ko, N., Eom, H., Kim, J., Lee, J.W., Jin, D.I., Kim, H. :
Production of heterozygous alpha 1,3-galactosyltransferase (GGTA1) knock-out transgenic miniature pigs expressing human CD39. Transgenic Res :, 2016. Pubmed reference: 27830476. DOI: 10.1007/s11248-016-9996-7.
Kang, J.T., Kwon, D.K., Park, A.R., Lee, E.J., Yun, Y.J., Ji, D.Y., Lee, K., Park, K.W. :
Production of α1,3-galactosyltransferase targeted pigs using transcription activator-like effector nuclease-mediated genome editing technology. J Vet Sci 17:89-96, 2016. Pubmed reference: 27051344. DOI: 10.4142/jvs.2016.17.1.89.
Petersen, B., Frenzel, A., Lucas-Hahn, A., Herrmann, D., Hassel, P., Klein, S., Ziegler, M., Hadeler, K.G., Niemann, H. :
Efficient production of biallelic GGTA1 knockout pigs by cytoplasmic microinjection of CRISPR/Cas9 into zygotes. Xenotransplantation 23:338-46, 2016. Pubmed reference: 27610605. DOI: 10.1111/xen.12258.
Priori, D., Colombo, M., Koopmans, S.J., Jansman, A.J., van der Meulen, J., Trevisi, P., Bosi, P. :
The A0 blood group genotype modifies the jejunal glycomic binding pattern profile of piglets early associated with a simple or complex microbiota. J Anim Sci 94:592-601, 2016. Pubmed reference: 27065129. DOI: 10.2527/jas.2015-9948.
2013 Bradstreet, R.W., Toledo-Pereyra, L.H. :
Mechanisms of Gal-knockout pig cell selection for somatic cell nuclear transfer. J Surg Res :, 2013. Pubmed reference: 23499396. DOI: 10.1016/j.jss.2013.02.007.
Li, P., Estrada, J.L., Burlak, C., Tector, A.J. :
Biallelic knockout of the α-1,3 galactosyltransferase gene in porcine liver-derived cells using zinc finger nucleases. J Surg Res 181:e39-45, 2013. Pubmed reference: 22795272. DOI: 10.1016/j.jss.2012.06.035.
Liu, Y., Yang, J.Y., Lu, Y., Yu, P., Dove, C.R., Hutcheson, J.M., Mumaw, J.L., Stice, S.L., West, F.D. :
α-1,3-Galactosyltransferase Knockout Pig Induced Pluripotent Stem Cells: A Cell Source for the Production of Xenotransplant Pigs. Cell Reprogram 15:107-16, 2013. Pubmed reference: 23402576. DOI: 10.1089/cell.2012.0062.
Miyagawa, S., Maeda, A., Takeishi, S., Ueno, T., Usui, N., Matsumoto, S., Okitsu, T., Goto, M., Nagashima, H. :
A lectin array analysis for wild-type and α-Gal-knockout pig islets versus healthy human islets. Surg Today :, 2013. Pubmed reference: 23549931. DOI: 10.1007/s00595-013-0569-6.
Shimatsu, Y., Yamada, K., Horii, W., Hirakata, A., Sakamoto, Y., Waki, S., Sano, J., Saitoh, T., Sahara, H., Shimizu, A., Yazawa, H., Sachs, D.H., Nunoya, T. :
Production of cloned NIBS (Nippon Institute for Biological Science) and α-1, 3-galactosyltransferase knockout MGH miniature pigs by somatic cell nuclear transfer using the NIBS breed as surrogates. Xenotransplantation :, 2013. Pubmed reference: 23581451. DOI: 10.1111/xen.12031.
Xin, J., Yang, H., Fan, N., Zhao, B., Ouyang, Z., Liu, Z., Zhao, Y., Li, X., Song, J., Yang, Y., Zou, Q., Yan, Q., Zeng, Y., Lai, L. :
Highly efficient generation of GGTA1 biallelic knockout inbred mini-pigs with TALENs. PLoS One 8:e84250, 2013. Pubmed reference: 24358349. DOI: 10.1371/journal.pone.0084250.
2012 Burlak, C., Wang, Z.Y., Chihara, R.K., Lutz, A.J., Wang, Y., Estrada, J.L., Tector, A.J. :
Identification of human preformed antibody targets in GTKO pigs. Xenotransplantation 19:92-101, 2012. Pubmed reference: 22497511. DOI: 10.1111/j.1399-3089.2012.00695.x.
Ekser, B., Bianchi, J., Ball, S., Iwase, H., Walters, A., Ezzelarab, M., Veroux, M., Gridelli, B., Wagner, R., Ayares, D., Cooper, D.K. :
Comparison of hematologic, biochemical, and coagulation parameters in α1,3-galactosyltransferase gene-knockout pigs, wild-type pigs, and four primate species. Xenotransplantation 19:342-54, 2012. Pubmed reference: 23145497. DOI: 10.1111/xen.12007.
Fang, J., Walters, A., Hara, H., Long, C., Yeh, P., Ayares, D., Cooper, D.K., Bianchi, J. :
Anti-gal antibodies in α1,3-galactosyltransferase gene-knockout pigs. Xenotransplantation 19:305-10, 2012. Pubmed reference: 22970769. DOI: 10.1111/j.1399-3089.2012.00710.x.
2011 Ekser, B., Gridelli, B., Veroux, M., Cooper, D.K. :
Clinical pig liver xenotransplantation: how far do we have to go? Xenotransplantation 18:158-67, 2011. Pubmed reference: 21696445. DOI: 10.1111/j.1399-3089.2011.00642.x.
Hara, H., Koike, N., Long, C., Piluek, J., Roh, D.S., SundarRaj, N., Funderburgh, J.L., Mizuguchi, Y., Isse, K., Phelps, C.J., Ball, S.F., Ayares, D.L., Cooper, D.K. :
Initial in vitro investigation of the human immune response to corneal cells from genetically engineered pigs. Invest Ophthalmol Vis Sci 52:5278-86, 2011. Pubmed reference: 21596821. DOI: 10.1167/iovs.10-6947.
Nguyen, D.T., Choi, H., Jo, H., Kim, J.H., Dirisala, V.R., Lee, K.T., Kim, T.H., Park, K.K., Seo, K., Park, C. :
Molecular characterization of the human ABO blood group orthologus system in pigs. Anim Genet 42:325-8, 2011. Pubmed reference: 21554350. DOI: 10.1111/j.1365-2052.2010.02152.x.
Thompson, P., Badell, I.R., Lowe, M., Cano, J., Song, M., Leopardi, F., Avila, J., Ruhil, R., Strobert, E., Korbutt, G., Rayat, G., Rajotte, R., Iwakoshi, N., Larsen, C.P., Kirk, A.D. :
Islet xenotransplantation using gal-deficient neonatal donors improves engraftment and function. Am J Transplant 11:2593-602, 2011. Pubmed reference: 21883917. DOI: 10.1111/j.1600-6143.2011.03720.x.
2010 Martínez-Alarcón, L., Ramis, G., Majado, M.J., Quereda, J.J., Herrero-Medrano, J.M., Ríos, A., Ramírez, P., Muñoz, A. :
ABO and RH1 blood group phenotyping in pigs (Sus scrofa) using microtyping cards. Transplant Proc 42:2146-8, 2010. Pubmed reference: 20692429. DOI: 10.1016/j.transproceed.2010.05.105.
2009 Yeom, SC., Oh, BC., Cho, SY., Park, CG., Lee, BC., Lee, WJ. :
Investigation of blood typing method for seoul National University miniature pig. Transplant Proc 41:1921-6, 2009. Pubmed reference: 19545757. DOI: 10.1016/j.transproceed.2009.01.096.
2008 Fujimura, T., Murakami, H., Kurome, M., Takahagi, Y., Shigehisa, T., Nagashima, H. :
Effects of recloning on the efficiency of production of alpha 1,3-galactosyltransferase knockout pigs. J Reprod Dev 54:58-62, 2008. Pubmed reference: 18094530.
2002 Lai, L., Kolber-Simonds, D., Park, K.W., Cheong, H.T., Greenstein, J.L., Im, G.S., Samuel, M., Bonk, A., Rieke, A., Day, B.N., Murphy, C.N., Carter, D.B., Hawley, R.J., Prather, R.S. :
Production of alpha-1,3-galactosyltransferase knockout pigs by nuclear transfer cloning. Science 295:1089-92, 2002. Pubmed reference: 11778012. DOI: 10.1126/science.1068228.
2001 Yamamoto, F., Yamamoto, M. :
Molecular genetic basis of porcine histo-blood group AO system Blood 97:3308-3310, 2001. Pubmed reference: 11342465.
2000 Kobayashi, T., Yokoyama, I., Nagasaka, T., Namii, Y., Hayashi, S., Liu, D., Oikawa, T., Usami, T., Morozumi, K., Yamada, K., Haba, T., Tominaga, Y., Uchida, K., Takagi, H. :
Efficacy of double filtration plasmapheresis pretreatment in clinical ABO-incompatible transplantation and experimental pig-to-baboon xenotransplantation. Transplant Proc 32:57, 2000. Pubmed reference: 10700967.
1964 Rasmusen, B.A. :
Gene interaction and the A-O blood group system in pigs Genetics 50:191-198, 1964. Pubmed reference: 14191350.
1962 Andresen, E. :
Blood groups in pigs Annals of the New York Academy of Sciences 97:207-225, 1962. Pubmed reference: 13861461.
Saison, R., Ingham, D.G. :
A report on blood groups in pigs Annals of the New York Academy of Sciences 97:226-232, 1962. Pubmed reference: 14496091.
1958 Sprague, L.M. :
On the Recognition and Inheritance of the Soluble Blood Group Property "Oc" of Cattle. Genetics 43:906-12, 1958. Pubmed reference: 17247803.
1949 Chadwick, D.W., Smith, H. :
Serological characters of hog gastric mucin. Nature 164:61, 1949. Pubmed reference: 18133537.

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