Olga O. Blumenfeld & Santosh K. Patnaik

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Phenotypes in the World of Blood Group Antigens
documented in the Database of DNA Variation in
Genes Encoding Blood Group Antigens
Olga O. Blumenfeld Santosh K.
Patnaik Departments of Biochemistry (OOB) Cell
Biology (SKP) Albert Einstein College of
Medicine, New York www.bioc.aecom.yu.edu/bgmut/in
dex.htm
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Blood Group Antigens
proteins, glycans or glycolipids variety of
functions expressed at the surface of red cells
polymorphic in the population
Y
Y
Y


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Blood Group System

• A set of variant antigens
• resulting from alleles of a single locus,
• each defining a common serological phenotype.

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Summary 29 blood group systems, 40 genes, 707
alleles Also detailed non-human counterparts for
H/h, MN, Rh
System Locus Funcion Alleles ABO ABO
enzyme 115 Chido- Rodgers C4A,
factor 7 C4B Colton AQP1 channel 7 Cromer DAF
receptor 13 Diego SLC4A1 exchanger
78 Dombrock DO unknown 9 Duffy FY receptor 7 Gerb
ich (Ge) GYPC structure 9 GIL AQP3 channel 2 H/h
FUT1, enzymes 57 FUT2 I GCN2 enzyme 8 (IGnT)
Indian (IN) CD44 adhesion 2 JMH
SEMA7A signaling 0 Kell (with
Kx) KEL, enzyme 67 XK Kidd SLC14A1 transport 8
Knops CR1 receptor 24
System Locus Function Alleles Landsteiner- ICAM4
adhesion 3 Weiner (LW) Lewis FUT3, enzymes 36
FUT6, FUT7 Lutheran LU adhesion 16 MNS GYPA,
unknown 43 GYPB, GYPE OK BSG adhesion 5 P-rel
ated A4GALT, enzymes 27 B3GALT3 RAPH-MER2
CD151 3 Rh RHCE, transpo
rt 126 RHD, RHCG RHAG, RHBG Scianna ERMAP adh
esion 4 Xg XG, adhesion 0 CD99
(MIC2) YT ACHE enzyme 4
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Summary of DNA alterations
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Phenotype vs genotype
A number of alleles give rise to the same blood
group phenotype Silencing mutations nonsens
e, deletions, insertions, splicing, regulatory
regions rearrangements, gross deletions (null
phenotype in nearly all systems) Kell, Rh,
Diego, ABO, others Gene rearrangements
GYPA, Rh ex. Sta - 7 genotypes RH neg - 17
genotypes A single allele gives rise to a unique
blood group phenotype Missense
mutations Kell, Diego, RH, Duffy, ABO and
others Gene rearrangements GYPA,
Miltenberger series Rh, weak D(Du), DAU
others
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Same Blood Group Phenotype, Multiple
Genotypes Kell null 1 phenotype 11
genotypes 7 nonsense 3 splicing 1 deletion
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Same Blood Group Phenotype, Multiple Genotypes
O gene-null Same deletion in many alleles
(261delG in 38 of 43 O null alleles)
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Band 3 Glycoprotein
anion exchanger
19 blood group phenotypes 54 other phenotypes
(spherocytosis, etc.)
del
19 variants
Binds torbc cytoskeleton
anion ex.
del
Popov et al. JBC.1997,272,18325
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Multiple Blood Group Phenotypes, Multiple
Genotypes
Diego 19 of 19 alleles
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Sites and distribution of alterations vs location
of epitopes Kell (KEL)
Each polymorphic site can be assigned to a
different Kell antigen 24 missense mutations at
positions in extracellular domains 7 nonsense 3
splicing 1 del Sets of polymorphic
residues Each expressed in different individuals
at different frequencies. Common phenotype K-1,
2 -3, -21, 4 -6, 7 11, -17 14, -24 10,
5, 12, 13, 16, 18, 20, 22, -23 Known
antithetical partners K2/K1 K4/K3/K21 K7/K6
K11/K17
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The Kell Glycoprotein
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Single Blood Group Phenotype, Single Genotype
Kell 22 of 24 alleles
note
note
note
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Same Blood Group Phenotype, Multiple
Genotypes Examples in the KEL blood group system
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Single Blood Group Phenotype, Single Genotype
Rh
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Examples of genotypes vs phenotypes due to DNA
rearrangements in GYPA family

• Gene Sequence Phenotype
• GYPA ex3 EET ex4 GERVQL wild type
• GYPB ex2 QTN ex4 GETGQL wild type s
• GYPB ex2 QTN ex4 GEMGQL wild type S
• hyb.A-Bs Recombination ex3 EET ex4 GETGQL HIL
• hyb.A-BS Recombination ex3 EET ex4 GEMGQL
  SJLhyb.BAB Gene conversion ex3 EET ex4
  GETGQL HIL
• hyb.B-A Recombination ex2 QTN ex4 GERVQL Sta
• Johe,Vengelen-Tyler,Leger,Blumenfeld Blood
  1991,782456

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Examples were provided showing that, on the red
cell surface, single amino acid or carbohydrate
alterations, resulting from missense mutations
or other DNA changes are recognized, as one might
expect, as foreign by the immune system and,
remarkably, can be detected by serological
approaches .
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Acknowledgements
Contributors to the database Departments of
Biochemistry and Cell Biology, Albert Einstein
College of Medicine Thank you!