title: Lack of the nucleoside transporter ENT1 results in the Augustine-null blood type and ectopic mineralization.
abstract: The Augustine-negative alias At(a-) blood type, which seems to be restricted to people of African ancestry, was identified half a century ago but remains one of the last blood types with no known genetic basis. Here we report that a nonsynonymous single nucleotide polymorphism in SLC29A1 (rs45458701) is responsible for the At(a-) blood type. The resulting p.Glu391Lys variation in the last extracellular loop of the equilibrative nucleoside transporter 1 (ENT1; also called SLC29a1) is known not to alter its ability to transport nucleosides and nucleoside analog drugs. Furthermore, we identified 3 individuals of European ancestry who are homozygous for a null mutation in SLC29A1 (c.589+1G>C) and thus have the Augustine-null blood type. These individuals lacking ENT1 exhibit periarticular and ectopic mineralization, which confirms an important role for ENT1/SLC29A1 in human bone homeostasis as recently suggested by the skeletal phenotype of aging Slc29a1(-/-) mice. Our results establish Augustine as a new blood group system and place SLC29A1 as a new candidate gene for idiopathic disorders characterized with ectopic calcification/mineralization.
authors.affiliation: International Blood Group Reference Laboratory, National Health Service Blood and Transplant, Bristol, United Kingdom;
authors.forename: Geoff
authors.initials: G
authors.lastname: Daniels
authors.affiliation: Department of Biology, University of Vermont, Burlington, VT;
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Ballif
authors.affiliation: Institut National de la Transfusion Sanguine, Paris, France;
authors.forename: Virginie
authors.initials: V
authors.lastname: Helias
authors.affiliation: Institut National de la Transfusion Sanguine, Paris, France;
authors.forename: Carole
authors.initials: C
authors.lastname: Saison
authors.affiliation: International Blood Group Reference Laboratory, National Health Service Blood and Transplant, Bristol, United Kingdom;
authors.forename: Shane
authors.initials: S
authors.lastname: Grimsley
authors.affiliation: Centre Régional de Transfusion Sanguine de Lille, Lille, France;
authors.forename: Lucienne
authors.initials: L
authors.lastname: Mannessier
authors.affiliation: Blood Transfusion Service, Swiss Red Cross, Berne, Switzerland;
authors.forename: Hein
authors.initials: H
authors.lastname: Hustinx
authors.affiliation: Red Cell Immunohaematology Laboratory of Colindale, London, United Kingdom; and.
authors.forename: Edmond
authors.initials: E
authors.lastname: Lee
authors.affiliation: Institut National de la Transfusion Sanguine, Paris, France;
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cartron
authors.affiliation: Institut National de la Transfusion Sanguine, Département Centre National de Référence pour les Groupes Sanguins, Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Peyrard
authors.affiliation: Institut National de la Transfusion Sanguine, Paris, France;
authors.forename: Lionel
authors.initials: L
authors.lastname: Arnaud
mesh_terms: D000818:Animals; D001789:Blood Group Antigens / Q000235:genetics* / Q000378:metabolism; D033721:Equilibrative Nucleoside Transporter 1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009999:Ossification, Heterotopic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D017433:Protein Structure, Secondary; D044465:White People
chemical_list: D001789:Blood Group Antigens; D033721:Equilibrative Nucleoside Transporter 1; C438649:SLC29A1 protein, human; C498476:SLC29A1 protein, mouse