Names for MNS Blood Group Alleles

Transcription

1 Names for MNS Blood Group Alleles General description: The MNS blood group system consists of 46 antigens carried on glycophorin A (GPA), glycophorin B (GPB) or on hybrids of these glycophorins. These proteins are single pass type I membrane glycoproteins that are heavily O-glycosylated. GPA carries an N- glycan. GPA consists of 131 amino acids, GPB of 7 amino acids and both have a leader sequence of 19 amino acids that is cleaved from the membrane bound protein. The hybrid proteins vary in length based on their composition but also have a 19 amino acid leader sequence. GPA is encoded by GYPA, GPB by GYPB. A third gene in this family, GYPE, normally does not encode detectable protein at the red cell surface but the gene has been shown to be involved in some gene rearrangements that encode cell-surface borne hybrid proteins. As described above, the proteins are encoded by GYPA or GYPB, or MNS if analysis is to predict a blood group antigen. Gene name: GYPA GYPB GYPE Number of exons: 7 5 plus 1 pseudoexon 4 plus pseudoexons Initiation Exon Exon Exon codon: Stop codon: Exon 7 Exon 6 Exon 6 GenBank #: NM_00099 NM_00100 NM_0010 Entrez GeneID: Exon numbering accounts for the presence of pseudoexons in GYPB and GYPE. Thus, GYPB pseudoexon 3 corresponds to the GYPA exon 3 sequence. This GYPB pseudoexon is involved in many gene rearrangements encoding hybrid glycophorins in this blood group system. Similarly, GYPE pseudoexons 3 and 4 correspond to GYPA exon 3 and 4 sequences. These GYPE pseudoexons are involved in gene rearrangements encoding hybrids. Reference allele for GYPA: Accession number: Preferred: Acceptable: Reference allele for GYPB: Accession number: Preferred: Acceptable: L31860 GYPA*01 GYPA*01, GYPA*M or M if inferred by hemagglutination J098 GYPB*04 GYPB*04, GYPB*s or s if inferred by hemagglutination Page 1 of 10

2 Table 1. MNS alleles with single nucleotide polymorphisms that generate blood group antigens. A. GYPA: Reference allele MNS*01 encodes M, En a, ENEH, ENEP, ENAV, ENDA, ENEV. Note: In most cases, the nucleotide changes also can occur on an N allele; these nucleotide changes are not given. Phenotype Allele name Nucleotide change Intron/ Exon MNS:1 or M+ MNS: N+ MNS:1,-,8 M c + MNS:7,9, 40 Vw+ MNS:-1,-,11 M g + MNS:1 Vr+ MNS:14 Mt(a+) MNS:16 Ri(a+); GYPA*01 Amino acid change GYPA*M 59C; 71G; 7T Ser0, Gly4 GYPA*0 GYPA*N 59C>T; 71G>A; 7T>G Ser0Leu, Gly4Glu GYPA*08 GYP.Mc 71G>A,7T>G Gly4Glu GYPA*09 GYPA*Vw 140C>T 3 Thr47Met GYPA*11 GYPA*Mg 68C>A Thr3Asn GYPA*1 GYPA*Vr 197C>A 3 Ser66Tyr GYPA*14 GYPA*Mta 30C>T 3 Thr77Ile GYPA*16 GYPA*Ria 6G>A 3 Glu76Lys MNS:18 Ny(a+) GYPA*18 138T>A 3 Gln46Glu MNS:7,19, 40 Hut+ MNS:31 Or+ MNS:37 ERIK+ GYPA*19 GYPA*Hut 140C>A 3 Thr47Lys GYPA*31 GYPA*Or 148C>T 3 Arg50Trp GYPA*37 GYPA*ERIK 3G>A 4 Gly78Arg MNS:38 GYPA*38 17C>T 3 Pro73Ser Comments See alsogyp.ebh in hybrid table Page of 10

3 Phenotype Allele name Nucleotide change Intron/ Exon Os(a+) GYPA*Osa MNS: 39,41 HAG+ MNS: 4,43 MARS+ GYPA*41 GYPA*HAG 50G>C 4 Ala84Pro GYPA*43 GYPA*MARS 44C>A 4 Glu8Lys MNS: 45 ENEV GYPA* 45 4T>G 4 Val81Gly MNS:46 MNTD+ GYPA*46 GYPA*MNTD 107C>G 3 Thr36Arg Amino acid change Comments Most anti-m but only few anti-n react with M c + RBCs Page 3 of 10

4 Table 1. MNS alleles with single nucleotide polymorphisms that generate blood group antigens. B. GYPB: Reference allele GYPB*04 encodes N, s. Expression of the U antigen involves GPB and another protein, probably RhAG. Phenotype Allele name Nucleotide change MNS:4 s+ MNS :3 S+ MNS:6 s+, He+ MNS:3,6 S+, He+ GYPB*04 GYPB*s Intron/ Exon GYPB*03 GYPB*S 143C>T 4 Thr48Met GYPB*06.01 GYPB* T>G, 60A>G, 67A>T, 71A>G, 7G>T 59T>G, 60A>G, 67A>T, 71A>G, 7G>T, 143C>T MNS:1 M v + GYPB*1 65C>G ThrSer MNS:4 Mit+ GYPB*4 161G>A 4 Arg54His MNS:3 S D + GYPB*3 173C>G 4 Pro58Arg MNS: 3,5W S U+ w MNS: 3,5W S U+ w GYPB*03N.01 GYPB.NY GYPB*03N.0 GYP.He(NY) 143C>T 08G>T; 30C>T; 51C>G; 59T>G; 60A>G; 67A>T; 71A>G; Amino acid change Leu0Trp, Thr3Ser, Glu4Gly; Leu0Trp, Thr3Ser, Glu4Gly; Thr48Met Thr48Met, Ser84Thr Leu0Trp, Thr3Ser, Glu4Gly, Comments Page 4 of 10

5 Phenotype Allele name Nucleotide change MNS: 3,5W S U+ w MNS: 3,5W S U+ w GYPB*03N.03 GYPB.P GYPB*03N.04 GYP.He(P) 7G>T; 143C>T; 08G>T; 30C>T; 51C>G Intron/ Exon C>T; 4 Intron 5+5g>t 59T>G; 60A>G; 67A>T; 71A>G; 7G>T; 143C>T ; 4; Intron 5 +5g>t Amino acid change Thr48Met, Ser84Thr Thr48Met Leu0Trp, Thr3Ser, Glu4Gly, Thr48Met Comments Page 5 of 10

6 Table. MNS alleles created by gene rearrangement events within the GYPA gene family A: parent allele GYPA. Phenotype Allele name Nucleotide Protein Comments GYP(A-A) hybrid series MNS:15 St(a+), MNS:15 St(a+) MNS:15 St(a+) MNS:6,15 He+, St(a+) GYP(A-B) series MNS:- 3,4,0,34 S-s+, Hil+, MINY+ MNS:3,- 4,3,33 S+s-, TSEN+, MINY+ MNS:-1,,-3,- 4,-5,36 M-N+S-s-U-, SAT+ GYP(A-B-A) series GYP* GYP.Zan GYP*101.0 GYP.EBH GYP* GYP.Mar GYP* GYP.Cal GYP*01.01 GYP.Hil GYP*0.01 GYP.JL GYP*03.01 GYP.SAT GYPA del exon 3 GPA del46-77 GYP(A1--BΨ3-A4-7) GYPA 3G>A del exon 3 GPA del46-77 Nucleotide change at 3 destabilises normal splicing. St a is encoded by a GYPA transcript that lacks exon 3. Full-length transcript encodes ERIK (MNS37; see table 1). GYPA del exon 3 GPA del46-77 GYP(A1--EΨ3-A4-7) GYPA 58G>T, 67A>T GPA Gly0Trp, Thr3Ser GPA del GYP(A1-3 B33-31) GP(A1-77-B78-104) GYP(A1-3 B33-31) 39C>T GYP(A1-71 B7-369) 59C>T; 71G>A; 7T>G GP(A1-77-B78-104) Thr80Met GYPA(1-90-B91-13) Ser0Leu, Gly4Glu GYP(A1--BΨ3-A4-7) breakpoint in intron 4 not defined Previously GYP.TK Page 6 of 10

7 Phenotype Allele name Nucleotide Protein Comments MNS:10,3 Mur +, Dane+ MNS:10,3, 44 Mur +, Dane+, ENDA MNS:6, 7 Hop+,Nob+ MNS: 6,7 Hop,Nob+ MNS:0, 34 Hil+, MINY GYP.Vw Numbers have not been assigned to these GYP.Hut alleles in this series and they are included in table 1. It has been proposed that they are GYP.Mc derived from hybrid genes but the crossover GYP.Mg points have not been determined experimentally. GYP* GYP.Dane GYP*301.0 GYP.Dane GYP*30.01 GYP.Joh GYP*30.0 GYP.Nob GYP*303 GYP.KI GYP(A1-159 BΨ A ); 191T>A GYP(A1-159 BΨ A ) GYP(A1-0 BΨ03 A04-450) GYP(A1-0 BΨ03-1 A13-450) 03G>C; 1A>C GYP(A1-38 B39-4 A43-450) 39G>C; 4T>G GP(A1-5-B53-58-A59-149); Ile46Asn GP(A1-5-B53-58-A59-149) GPA(1-67)-B(68)-GPA(69-150) Arg68Thr GPA(1-67)-B(68-7)-GPA(73-150) Arg68Thr; Tyr71Ser GPA(1-79)-B(80-81)-GPA(8-150) Arg80Thr;Val81Gly Also expresses Mur antigen Also expresses Mur antigen; does not express ENDA Gene conversion in exon 3 replaces GYPA nucleotide 03 with the corresponding nucleotide from GYPBΨ3. This is the minimum but the breakpoint is not defined. Gene conversion in exon 3 replaces GYPA nucleotides (03-1) with corresponding nucleotides from GYPBΨ3. This is the minimum but the breakpoint is not defined. Gene conversion in exon 4 replaces GYPA nucleotides (39-4) with corresponding nucleotides from GYPB. This is the minimum but the breakpoint is not defined. Page 7 of 10

8 Table. MNS alleles created by gene rearrangement events within the GYPA gene family: B: parent allele GYPB Phenotype Allele name Nucleotide Amino acid Comments GYP(B-A) hybrid series MNS:15 St(a+) MNS: 3,4,4 Dantu+ GYP(B-A-B) hybrid series MNS: 3,4,8,10,0,34,35 S s+, Mi(a+), Mur+, Hil+, MUT+, MINY+ MNS:3, 4,8,10,6,33,3 4,35 S+s, Mi(a+), Mur+, Hop+, TSEN+, MUT+, MINY+ MNS: 3,4,8,10,0,6 34,35 S s+, Mi(a+), Mur+, Hil+, MUT+, MINY+ MNS: 3,4,8, 0,34,35 S s+, Mi(a+), GYP*401 GYP.Sch GYP.40 GYP.Dantu GYP.501 GYP.Mur GYP.50 GYP.Hop GYP.503 GYP.Bun GYP.504 GYP.HF GYP(B1-136-A ) GPB(1-46)-A(47-118) Reciprocal product is GYP.Hil GYP(B1-175-A ) GPB(1-58)-A(59-118) Reciprocal product is GYP.Tk GYP(B1-136-Bψ A05-9-B30-366) GYP(B1-136-Bψ A05-9-B30-366) 36C>G GYP(B1-136-Bψ A11-9-B30-366) GYP(B1-136-Bψ A160-3-B33-369) GP(B1-69-A B78-1) GPB s ins DKHKRDTYPAHTAN EVSEISVRTVYPPEE ET GP(B1-69-A B78-1) GPB S ins DKHKRDTYPAHTAN EVSEISVRTVYPPEE ET Thr80Met GP(B1-71-A7-77- B78-1) GPB s ins DKHKRDTYPAHTAN EVSEISVRTVYPPEE ET GP(B1-53-A B79-13) in GPB s Novel sequence derived from composite exon; GYPB 5' pseudoexon 3 + GYPA 3' exon 3 Novel sequence derived from composite exon; GYPB 5' pseudoexon 3 + GYPA 3' exon 3 Novel sequence derived from composite exon; GYPB 5' pseudoexon 3 + GYPA 3' exon 3 Novel sequence derived from composite exon; GYPB 5' pseudoexon 3 + GYPA 3' exon 3 Page 8 of 10

9 Phenotype Allele name Nucleotide Amino acid Comments Hil+, MUT+, MINY+ DKHKRDTYAATPRA HEVSEISVRTVYPPE EET46-77ins MNS: etc He+ GYP*505 GYP.He(GL) Page 9 of 10

10 Phenotype Allele name Nucleotide Amino acid Comments GYP deletion hybrids MNS: 1, En(a ) M N MNS: 3, 4, 5 S s U MNS: 1,, 3, 4, 5 M k M k M N S s GYPA*01N Del GYPA exons -7 : GYPB exon 1 GYPB*01N Del GYPB exons -5 ; GYPE exon 1 GYP*01N Del GYPA exons -7 ; GYPB exons 1-5 GPA absent GPB absent GPA and GPB absent Page 10 of 10