C O M M I T T E E R EBLOOD

P O RGROUP
T ANTIGEN AND GENE TERMINOLOGY

Terminology for blood group antigens and geneshistorical

origins and guidelines in the new millennium
G. Garratty, W. Dzik, P.D. Issitt, D.M. Lublin, M.E. Reid, and T. Zelinski

n 1901, Landsteiner named the first two blood group

antigens A and B, using the first two letters of the alphabet.1 RBCs not reacting with anti-A and anti-B
were called type C.1 In 1902, von Decastello and Sturli2
described RBCs reacting with both anti-A and anti-B but did
not give this type a name; they continued calling RBCs that
did not react with anti-A and anti-B type C. In a publication
in 1910,3 Landsteiner showed serologic results of all four
ABO types but did not use the terms O and AB. In 1911, von
Dungern and Hirszfeld4 appear to be the first to use the term
O to describe RBCs not reacting with anti-A and anti-B and the
term AB for RBCs reacting with both anti-A and anti-B. The
lack of A and B was indicated by the letter "O", but it is controversial whether this letter should have been printed as a
zero (0) or whether the letter O came from the first letter of
the German word "ohne" meaning without (i.e., without A
or B). The letter O was commonly used in print and speech,
and, almost 100 years later, the ISBT Working Party on Terminology for Red Cell Surface Antigens has recommended
that we continue to use the letter O.5

ABBREVIATIONS: HGM = Human Gene Mapping (Nomenclature Committee); ISGN = International System for Gene Nomenclature; IVS = intron intervening sequence; nt(s) = nucleotide(s).
From the American Red Cross Blood Services, Southern California Region, Los Angeles, California; Blood Transfusion Service,
Massachusetts General Hospital, Boston, Massachusetts; Transfusion Service, Duke University Medical Center, Durham, North
Carolina; the Department of Pathology, Washington University
School of Medicine, St. Louis, Missouri; the Lindsley F. Kimball
Research Institute, New York Blood Center, New York, New
York; and the Rh Laboratory, University of Manitoba, Winnipeg,
Manitoba, Canada.
Address reprint requests to: George Garratty, PhD, FRCPath,
American Red Cross Blood Services, Southern California Region,
1130 South Vermont Avenue, Los Angeles, CA 90006; e-mail:
garratty@usa.redcross.org.
Received for publication August 6, 1999; revision received
and accepted August 17, 1999.
TRANSFUSION 2000;40:477-489.

Many readers may not realize that there were problems

with ABO terminology during the several decades following Landsteiners discovery. In 1907, Jansky6 proposed using Roman numerals I, II, III, and IV for O, A, B, and AB, respectively. In 1910, Moss7 (in the United States), who had
not read Janskys article, which appeared in an obscure
Czech journal, also, independently, suggested using Roman
numerals. Unfortunately, Moss suggested IV for group O
and I for group AB, a reversal of Janskys terms. For some
years, both numerical terminologies were popular: Mosss
nomenclature was popular in the United Kingdom, France,
and some parts of the United States, while Janskys system
was popular in other parts of the United States and elsewhere. In 1921, the American Association of Immunology,
the Association of Pathologists and Bacteriologists, and the
Society of American Bacteriologists made a joint recommendation that, on the basis of priority,...the Jansky classification be adopted.8(p130) Because of the continuing confusion, Landsteiner suggested in 19279 the universal use of
the symbols A, B, O, and AB, instead of Roman numerals.
Nevertheless, it is noteworthy that results of a survey published in 192910 indicated that 71 percent of 552 North
American hospitals were still using the Moss terminology,
16.5 percent used the Jansky terminology, 2.9 percent used
both, and only 4.7 percent used the Landsteiner terminology. Mosss terminology, often combined with letters (e.g.,
OIV, AII), persisted into the early 1950s in some areas.
After the discovery of the Rh system in 1940,11 the nomenclature problem became acute, again because of two
different terminologies, the CcDdEe terms of Fisher and
Race12 and Race and Sanger13 and the Rh/Hr terms used by
Wiener14 and his followers. Thus, in Europe, it was anti-D, -c, -e,
etc., and, in most of the United States it was anti-Rho, -hr,
-hr, etc. A fascinating review of the history of this controversy has been published.15
A popular way of naming blood group systems was to
use all or part of the name of the first antibody maker, or
reactive donor (journals such as TRANSFUSION will allow
this now only if there is written permission from the patient
or donor). For instance, Lewis, Duffy, Scianna, Dombrock,
Colton, Gerbich, Cromer, Knops, and Diego were the names

Volume 40, April 2000 TRANSFUSION 477

GARRATTY ET AL.

of antibody makers. Lutheran should have been Lutteran,

which was the name of the donor of the first reactive Lu(a+)
RBCs; the original donor blood sample was incorrectly labeled (Tippett P, oral communication, June 1999). Some
blood group names came from part of the name or the initials of the antibody maker, such as Kell from Kelleher; JMH
from John Milton Hagen; LKE from Luke; Cs from Cost-Sterling; Bg from Bennett-Goodspeed; and Ch and Rg from
Chido and Rodgers. On the basis of agreements reached at
an international meeting of prominent scientists,16 superscript lower-case letters began to be used to describe new
antigens or alleles (e.g., Lea, Fya). Many other examples can
be found.17 The derivation of some of the symbols used for
the antigens or alleles is interesting. For instance, the Duffy
symbol (Fy) came from the last two letters of the antibody
makers name (Duffy), as the first two letters, D and Du, had
already been used. The Ok blood group system was named
from the family name (Kobutso) of the antibody (anti-Oka)
producer; Ko had already been used, so the first letters of
the name were reversed to Ok (Morel P, oral communication, June, 1999). Jk came from the initials of the baby (John
Kidd) who had hemolytic disease of the newborn, the child
of the antibody maker (Mrs. Kidd), as K had already been
used for Kell.18
Some of the miscellaneous derivations of names of blood
groups are also fascinating. M and N were named with the
second and fifth letters of the word immune, because the
antibodies were produced by immunizing rabbits with human RBCs, and it was thought that the first letter, I, might
be confused with the number 1.19 Although I was not used
by Levine and Landsteiner in 1927, it was used, in 1956, by
Wiener et al.20 to describe a high-incidence antigen reacting with a powerful cold agglutinin; the letter I was selected
to emphasize the high degree of individuality of blood
specimens failing to react with the patients serum at room
temperature. In 1948, Morgan and Watkins21 suggested
changing the terms anti-O and O substance to anti-H
and H substance (...the substance might better be called
H-substance in place of O-substance, as this would differentiate it as a hetero-genetic, basic or primary substance
common to the great majority of red cells irrespective of
their ABO group.). The name of another high-incidence
antigen (U) was derived from the almost universal distribution of the new blood factor.22(p1445) Sid (Sda) was the first
name of the Head of Maintenance of the Lister Institute in
London, whose RBCs were part of an in-house panel and
reacted strongly with antibodies that were eventually
named anti-Sda (Tippett P, oral communication, June, 1999).
The Indian blood group system was named because of
its association with antibody producers from India. A similar rationale was used for the Bombay (Oh) blood group, the
first examples of which were found in that city in India. The
name for the S antigen/antibody came from the city
(Sydney) where the first anti-S was discovered (Sanger R,

478 TRANSFUSION Volume 40, April 2000

oral communication, June 1999). Xg and XK were named

because of their association with the X chromosome; the g
in Xg stood for Grand Rapids (Michigan), the site of the discovery, and the K in XK for its more obvious association with
the Kell system. Because the first example of En(a) RBCs
reacted like enzyme-treated RBCs, Darnborough et al. suggested that they may have abnormal red cell envelope
structure (hence the choice of the symbol En), which may
be due to some enzyme abnormality.23(p253) A low-incidence determinant on Rh:33 RBCs with depressed C and/
or e was named FPTT, because three of the four propositi
worked for the French Post and Telegraphic Telecommunications.24 A partial D phenotype associated with FPTT was
named DFR, "because F is a mnemonic for FPTT, and since
a minimum of three letters is required for synonyms, R was
added to F to reflect the initial French connection.25(p616)
A few blood groups were named after the scientists who
discovered them. For instance, the Landsteiner-Wiener (LW)
system was so named because the original Rh antibody,
produced by Landsteiner and Wiener by injecting rabbits
and guinea pigs with RBCs from rhesus monkeys, and named
Rh (anti-Rho or anti-D) after rhesus monkey, was later found
to be different from human Rh antibodies (i.e., anti-D). The
original antibody produced in rabbits and guinea pigs was
found to be identical to human antibodies (anti-LW) that
reacted with almost all RBCs tested, but that reacted much
better with D+ than D RBCs; this antibody was named antiLW after Landsteiner and Wiener. T was named after Oluf
Thomsen of Copenhagen, who, in 1926, called the new antigen L (for Latency). L was later termed T, in honor of
Thomsen, by his assistant Friedenreich, who showed the
relationship of T to bacterial infection.26 The n of Tn came
from the French word nouvelle, for a new T antigen.27 Pr
came from protease-sensitive.28 The superscript T of IT
was used because maximal amounts of the antigen were
thought to be present during transition from i to I.29
In 1961 and 1962, Allen and Rosenfield30 and Rosenfield
et al.31 suggested a numerical nomenclature for the Kell and
Rh systems. The numerical nomenclature was intended to
allow investigators to report serologic findings without necessarily including genetic interpretations (D or Rho became
Rh1, C or rh became Rh2, etc., and D+c+e became Rh:1,4,
5, etc.). Rosenfield et al.31 allocated Rh1 to Rh25, and other
investigators have since allocated Rh26 to Rh52.17,32
The numerical terminology was extended to other systems, (e.g., Lutheran); new antigens were named with numbers instead of the traditional names of antibody makers.
Thus, the traditional/conventional/popular terminology
for antigens is a mixture of letters (e.g., Lea, Fya, K) and numbers (e.g., Rh29, Lu3, K11), with a few remaining names
(e.g., Evans, Crawford).17,32
In 1980, the ISBT set up a Working Party on Terminology for Red Cell Surface Antigens. It should be emphasized
that their mandate was to devise a uniform nomenclature

BLOOD GROUP ANTIGEN AND GENE TERMINOLOGY

that would be both eye- and machine-readable. Their first

report, in 1982, stated, The ISBT Working Party is not trying to change the nomenclature of the blood groups. Numbers assigned to specificities are proposed as standard alternatives to current alphabetical names in those circumstances
where numbers are necessary as in some computer
systems.33(p165)
The working party suggested using upper-case letters
and Arabic numbers for system and antigen codes. New
antigens named after the introduction of the terminology
use three to six upper-case letters (BOW, JONES, etc.). Each
system, collection, or series of antigens is given a number
(e.g., ABO system = 001) and each antigen within the system is given a number (e.g., A = 001, B = 002). Thus, in computer code, A is 001001 and B is 001002. Sinistral zeros may
be omitted so that A can be expressed as 1.1 and B as 1.2.
In the Rh system (004), D = 001, C = 002, E = 003, etc. Thus,
for the computer, D, C, and E are 004001, 004002, and
004003, respectively. The system symbol and the antigen
number, minus the sinistral zeros, may be used (e.g., RH1,
RH2, RH3, respectively). Table 1 shows some of the alternatives. The full report of the ISBTWorking Party terms appears
elsewhere.5,34,35 Although all terms in Table 1 are acceptable,
TRANSFUSION chooses to use traditional terminology in
most cases.
In 1984 and 1992, Issitt and Crookston36 and Issitt and
Moulds37 published in TRANSFUSION advice regarding
terminology. These articles provided a basis for the terminology used by TRANSFUSION. In addition, the articles

TABLE 1. Blood group systems

System name
Traditional/ISBT
ABO
MNSs or MNS or MN
P
Rh
Lutheran
Kell
Lewis
Duffy
Kidd
Diego
Yt or Cartwright
Xg
Scianna
Dombrock
Colton
LW or LandsteinerWiener
Chido/Rodgers
Hh
Kx
Gerbich
Cromer
Knops
Indian
Ok
Raph

System symbol

ISBT number

Traditional

ISBT

001
002
003
004
005
006
007
008
009
010
011
012
013
014
015

ABO
MN
P
Rh
Lu
K
Le
Fy
Jk
Di
Yt
Xg
Sc
Do
Co

ABO
MNS
P1
RH
LU
KEL
LE
FY
JK
DI
YT
XG
SC
DO
CO

016
017
018
019
020
021
022
023
024
025

LW
Ch/Rg
H
Kx
Ge
Cromer
Kn
In
Ok
Raph

LW
CH/RG
H
XK
GE
CROM
KN
IN
OK
MER2

gave advice on the correct use of the English language in

connection with immunohematologic terms; examples of
common errors were given. This advice is still pertinent and
has been reemphasized by Issitt and Anstee in the first
chapter of their recently published textbook.17
Table 2 shows acceptable terms for blood group systems and antigens. The headings are the system names.
Under each system are listed the antigens. Traditional terms
are given first; ISBT terms are given in parentheses.Table 3
shows the ISBT collections of antigens. Once more, TRANSFUSION prefers to use traditional names (e.g., I and i rather
than I1 and I2). Tables 4 and 5 show low- and high-incidence
antigens by name and/or symbol. TRANSFUSION will usually use the symbol when describing these low- and highincidence antigens. Table 6 shows RBC antigens that are described in the literature and have traditional names but no
ISBT names or symbols.

TERMINOLOGY FOR GENES

In print, the symbol for a gene or gene cluster is usually italicized
(or underlined if italics are not possible). The traditional,17,32
ISBT,5,34,35 or International System for Gene Nomenclature
(ISGN)38-40 blood group symbols can be used (e.g., Fy, FY, or
DARC, respectively; Jk, JK, or SLC14A1, respectively).
Table 7 shows the terminology for blood group genes
that has been suggested (e.g., by ISBT) on the basis of serologic findings and that used by the Human Gene Mapping
(HGM) Nomenclature Committee (which formulated the
ISGN), which relates to known functional aspects of the
gene product. For instance, the ISGN uses FUT3 (fucosyl
transferase 3) for Le, DARC (Duffy antigen receptor for
chemokine) for Fy, SLC14A1 (solute carrier family 14, urea
transporter member 1) for Jk, SLC4A1 (solute carrier family 4, anion exchanger member 1) for Di, ACHE (acetylcholinesterase) for Yt, AQP1 (aquaporin) for Co, FUT1 (fucosyltransferase 1) for H, GYPC (glycophorin C) for Ge, DAF
(decay-accelerating factor) for Cromer, CR1 (complement
receptor 1) for Kn, CD44 for In, and CD147 for Ok. Such
functional terms will continually be changing. For instance,
the ISBT gene symbol for the Diego (DI) blood group system has not changed for years, but the ISGN name has
changed from DI to EPB3 (erythrocyte surface protein band
3) to AE1 (anion exchanger 1) to the present SLC4A1 (solute carrier family 4, anion exchanger member 1).
Although it may be difficult to remember two nomenclatures, there is merit in maintaining each system. For serologists, the ISBT designations are a reminder of the evolution of blood group science and the well-characterized
RBC antigens that are still determined today. For molecular biologists, the ISGN designations provide clues to the
character or function of a gene product. As the list of gene
designations is growing at a rapid pace, investigators should
contact the HGM Nomenclature Committee before nam-

Volume 40, April 2000 TRANSFUSION 479

GARRATTY ET AL.

TABLE 2. Blood group systems and antigens (ISBT symbols)

ABO (ABO) MNSs or MNS or MN (MNS)
M (MNS1)
N (MNS2)
S (MNS3)
s (MNS4)
U (MNS5)
He (MNS6)
Mia (MNS7)
Mc (MNS8)
Vw (MNS9)
Mur (MNS10)
Mg (MNS11)
Vr (MNS12)
Me (MNS13)
Mta (MNS14)
Sta (MNS15)
Ria (MNS16)
Cla (MNS17)
Nya (MNS18)
Hut (MNS19)
Hil (MNS20)
Mv (MNS21)
Far (MNS22)

Duffy (FY)

Kidd (JK)

Diego (DI)

Fya (FY1)
Fyb (FY2)
Fy3 (FY3)
Fy4 (FY4)
Fy5 (FY5)
Fy6 (FY6)

Jka (JK1)
Jkb (JK2)
Jk3 (JK3)

Dia (DI1)
Dib (DI2)
Wra (DI3)
Wrb (DI4)
Wda (DI5)
Rba (DI6)
WARR (DI7)
ELO (DI8)
Wu (DI9)
Bpa (DI10)
Moa (DI11)
Hga (DI12)
Vga (DI13)
Swa (DI14)
BOW (DI15)
NFLD (DI16)
Jna (DI17)
KREP (DI18)
Fra (DI20)
SW1 (DI21)

Chido/Rodgers
(CH/RG)
Ch1 (CH1)
Ch2 (CH2)
Ch3 (CH3)
Ch4 (CH4)
Ch5 (CH5)
Ch6 (CH6)
WH (CH7)
Rg1 (RG1)
Rg2 (RG2)

Hh (H)
H (H1)

P (P)

Rh (RH)

sD (MNS23)
P1 or P1 (P1)
Mit (MNS24)
Dantu (MNS25)
Hop (MNS26)
Nob (MNS27)
Ena (MNS28)
ENKT (MNS29)
'N' (MNS30)
Or (MNS31)
Dane (MNS32)
TSEN (MNS33)
MINY (MNS34)
MUT (MNS35)
SAT (MNS36)
ERIK (MNS37)
Osa (MNS38)
ENEP (MNS39)
ENEH (MNS40)
HAG (MNS41)
ENAV (MNS42)
MARS (MNS43)

A (ABO1)
B (ABO2)
A,B (ABO3)
A1 or A1
(ABO4)

Kx (XK)
Kx (XK1)

Yt or
Cartwright (YT)
Yta (YTI)
Ytb (YT2)

Gerbich (GE)
Ge2 (GE2)
Ge3 (GE3)
Ge4 (GE4)
Wb (GE5)
Lsa (GE6)
Ana (GE7)
Dha (GE8)

480 TRANSFUSION Volume 40, April 2000

D (RH1)
C (RH2)
E (RH3)
c (RH4)
e (RH5)
f (RH6)
Ce (RH7)
Cw (RH8)
Cx (RH9)
V (RH10)
Ew (RH11)
G (RH12)
Hro (RH17)
Hr (RH18)
hrs (RH19)
VS (RH20)
CG (RH21)
CE (RH22)
Dw (RH23)
c-like (RH26)
cE (RH27)
hrH (RH28)
Rh29 (RH29)

Xg (XG)

Lutheran (LU)

Goa (RH30)
hrB (RH31)
Rh32 (RH32)
Rh33 (RH33)
HrB (RH34)
Rh35 (RH35)
Bea (RH36)
Evans (RH37)
Rh39 (RH39)
Tar (RH40)
Rh41 (RH41)
Rh42 (RH42)
Craw (RH43)
Nou (RH44)
Riv (RH45)
Sec (RH46)
Dav (RH47)
JAL (RH48)
STEM (RH49)
FPTT (RH50)
MAR (RH51)
BARC (RH52)

Lua (LU1)
Lub (LU2)
Lu3 (LU3)
Lu4 (LU4)
Lu5 (LU5)
Lu6 (LU6)
Lu7 (LU7)
Lu8 (LU8)
Lu9 (LU9)
Lu11 (LU11)
Lu12 (LU12)
Lu13 (LU13)
Lu14 (LU14)
Lu16 (LU16)
Lu17 (LU17)
Aua (LU18)
Aub (LU19)
Lu20 (LU20)

Scianna (SC) Dombrock (DO)

Xga (XG1)

Sc1 (SC1)
Sc2 (SC2)
Sc3 (SC3)

Doa (DO1)
Dob (DO2)
Gya (DO3)
Hy (DO4)
Joa (DO5)

Cromer (CR)

Knops (KN)

Indian (IN)

Cra (CROM1)
Tca (CROM2)
Tcb (CROM3)
Tcc (CROM4)
Dra (CROM5)
Esa (CROM6)
IFC (CROM7)
WESa (CROM8)
WESb (CROM9)
UMC (CROM10)

Kna (KN1)
Knb (KN2)
McCa (KN3)
Sla (KN4)
Yka (KN5)

Ina (IN1)
Inb (IN2)

Kell (KEL)

Lewis (LE)

K (KEL1)
Lea (LE1)
k (KEL2)
Leb (LE2)
Kpa (KEL3)
Leab (LE3)
Kpb (KEL4)
LebH (LE4)
Ku (KEL5)
ALeb (LE5)
Jsa (KEL6)
BLeb (LE6)
Jsb (KEL7)
Ula (KEL10)
K11 (KEL11)
K12 (KEL12)
K13 (KEL13)
K14 (KEL14)
K16 (KEL16)
K17 or Wka
(KEL17)
K18 (KEL18)
K19 (KEL19)
Km (KEL20)
Kpc (KEL21)
K22 (KEL22)
K23 (KEL23)
K24 (KEL24)
VLAN (KEL25)
TOU (KEL26)

LW or LandsteinerColton (CO) Wiener (LW)

Coa (CO1)
Cob (CO2)
Co3 (CO3)

Ok (OK)
Oka (OK1)

LWa (LW5)
LWab (LW6)
LWb (LW7)

Raph (MER2)
Raph (MER2)

BLOOD GROUP ANTIGEN AND GENE TERMINOLOGY

Antigens of three blood group systems

(Chido/Rodgers, Rh, and MNS) are encoded by two homologous genes that are
COST
Ii
Er
GLOB
210
adjacent on the same chromosome. BeCsa (COST1)
I (I1)
Era (ER1)
P (GLOB1)
Lec
Csb (COST2)
i (I2)
Erb (ER2)
Pk (GLOB2)
Led
cause of this, the genes and gene prodLKE (GLOB3)
ucts of these systems can include hybrids. For the Chido/Rodgers blood
group system, the two common gene names and the enTABLE 4. Names and symbols of low-incidence
coded products are listed (Table 7). In the Rh system, both
antigens (ISBT 700 series)
the ISBT and the ISGN have adopted the terms RHD and
Name
Symbol
Number
RHCE to describe the genes that encode production of the
Batty
By
700.2
D antigen-bearing and the C- or c- plus E- or e-bearing proa
Christiansen
Chr
700.3
teins, respectively. When the gene involved is not known
Biles
Bi
700.5
Box
Bxa
700.6
(e.g., in the description of an Rh antigen not yet characterTraversu
Tra
700.8
ized at the molecular level) the term RH can be used. For
Radin
Rd
700.15
the MNS system, the ISBT gene name of MNS is used for
Torkildsen
Toa
700.17
Peters
Pta
700.18
both the genes and the two products (GPA and GPB): GPA
700.19
Reid
Rea
carries the M/N polymorphism and GPB carries the S/s
a
Jensen
Je
700.21
polymorphism. The ISGN names both genes (i.e., GYPA enLivesay
Lia
700.28
Milne
700.39
codes GPA and GYPB encodes GPB). A third gene in this
Rasmussen
RASM
700.40
family (GYPE) has not been shown conclusively to encode
Oldeide
Ola
700.43
its product (GPE) in the RBC membrane. The products of
JFV
700.44
Katagiri
Kg
700.45
each gene listed in Table 7 refer to all polymorphic forms,
Jones
JONES
700.47
the number of which ranges from 1 antigen (P, Hh, Ok, Raph
HJK
700.49
systems) to nearly 50 antigens (Rh system).
HOFM
700.50
TABLE 3. Antigens and ISBT symbols (ISBT names) of collections

SARA
LOCR
REIT

700.52
700.53
700.54

TABLE 5. Names and symbols of high-incidence

antigens (ISBT 901 series)
Name
Langereis
Augustine
Junior
John Milton Hagen
Anton
Sid
Duclos

Symbol
Vel
Lan
Ata
Jra
JMH
Emm
AnWj
Sda
Duclos
PEL
ABTI
MAM

Number
901.1
901.2
901.3
901.5
901.7
901.8
901.9
901.12
901.13
901.14
901.15
901.16

ing any gene (the names and contact information for the
appropriate HGM Nomenclature Committee members are
provided in White et al.40). Finally, it is important for investigators to realize that ISGN gene designations change as
more functional information becomes available. TRANSFUSION will continue to use traditional gene terminology
(e.g., Rh, Fy, Jk), but, when investigations are molecular in
nature, the ISGN symbols will sometimes be used in addition, in parentheses (e.g., Fy [DARC], Jk [SLC14A1]).

TERMINOLOGY FOR ALLELES

Alleles are alternative forms of a particular gene. Thus, they
are expressed by using the gene name and an appendage
that indicates the particular allele. For alleles, the ISGN uses
the gene name, followed by an asterisk and a letter or number in italics (e.g., RH*D, KEL*2, DARC*A).39 A space instead
of an asterisk is also sometimes used.38 Unfortunately, ISBT
uses numbers (e.g., LU*1) where ISGN uses letters (e.g.,
LU*A). Table 8 gives some examples of the three terminologies currently used. Table 9 shows the terminology for serologic phenotypes (traditional and ISBT).

NOMENCLATURE ASSOCIATED WITH

DNA-BASED TECHNOLOGY
Nucleic acids
DNA is made up of bases, the sugar 2-deoxyribose, and
phosphate groups. The bases are of two classes, pyrimidine
and purine. DNA is a helical polymer of deoxyribose linked
by phosphate groups; one of its four bases projects from
each sugar molecule of the sugarphosphate chain.
A base sugar is a nucleoside. A base sugarphosphate
unit is a nucleotide. Table 10 shows the one-letter abbreviations used. When bps are quantified, the terms kilo-bp (kbp)
and 1 million bp (Mbp) are sometimes used (e.g., a 235-bp
repeat sequence; a 47-kbp vector genome; 1 Mbp of DNA).

Volume 40, April 2000 TRANSFUSION 481

GARRATTY ET AL.

TABLE 6. RBC antigens described in the literature that have traditional but not ISBT names or symbols
MNSs or MNS or MN system
Kell system
Lewis system
Xg System
Cromer system
Knops system
Ii collection
GLOB collection
Independent lowincidence antigens
Independent highincidence antigens
Bg series
Pr series
Other antigens defined
by cold autoantibodies
Antigens involved in
polyagglutination

M1, Tm, MA, Sul, Sj, M, EnaTS, EnaFS, EnaFR, Shier, NA, UZ, UX, Can, UPS, UPR, Hu, Sext
RAZ
Lex, LebL, A1Led, BLed, ILebH
12E7, CD99
AM
McCb, Vil, Sieb
IF, ID, j, IH, IA, IB, iH, IT, IP1, ITP1, IP, IBH, IAB
p
SHIN, JAHK
Jca
Bga, Bgb, Bgc
Pr1h, Pr1d, Pr2, Pr3h, Pr3d, Pra, PrM, PrN
Gd1 (Sia-lb1), Gd2 (Sia-lb2), Sa, Fl(Sia-b1), Lud, Vo(Sia-l1), Li, Me, Om, Ju
T, Tn, Tk, Th, Tx, Tr, VA, Cad, HEMPAS, NOR, HbM

TABLE 7. Terminology for blood group system genes and gene products
Blood group

Gene symbols

system name

Traditional

ABO

ABO

ABO

ISBT

ABO

MNS

MN or MNSs

MNS

P
Rh

P1
Rh

Lutheran
Kell
Lewis
Duffy
Kidd
Diego
Yt
Xg
Scianna
Dombrock
Colton
Landsteiner-Wiener
Chido/Rodgers

Lu
K
Le
Fy
Jk
Di
Yt
Xg
Sc
Do
Co
LW
Ch/Rg

P1
RHD
RHCE
LU
KEL
LE
FY
JK
DI
YT
XG
SC
DO
CO
LW
CH/RG

Hh
Kx
Gerbich
Cromer
Knops
Indian
Ok
Raph

Hh
Kx
Ge
Cromer
Kn
In
Ok
Raph

H
XK
GE
CROM
KN
IN
OK
MER2

GYPA
GYPB
GYPE
P1
RHD
RHCE
LU
KEL
FUT3
DARC
SLC14A1
SLC4A1
ACHE
XG
SC
DO
AQP1
LW
C4A
C4B
FUT1
XK
GYPC
DAF
CR1
CD44
CD147
MER2

Sometimes the length of nucleotide molecules is qualified by

using the suffix mer (e.g., 20mer = 20 nucleotides).
A codon is a sequence of three nucleotides in a DNA
molecule that codes for an amino acid or biosynthetic message. Codons are also referred to as nucleotide triplets (e.g.,
CAT, ATC, ATT). Sequences of repeating nucleotides, also
known as tandem repeats, are indicated in parentheses with
n equaling the number of repeats (e.g., [TTAGGG]n, [GT]n).

482 TRANSFUSION Volume 40, April 2000

ISGN

Gene product name

3-N-acetyl-D-galactosaminyl transferase
-3-D-galactosyltransferase
Glycophorin A
Glycophorin B
Glycophorin E
Galactosyltransferase
RhD protein
RhCE protein
Lutheran glycoprotein and B-CAM
Kell glycoprotein
-3/4-L-fucosyltransferase
Fy glycoprotein
Urea Transporter
Anion exchanger 1 (band 3)
Acetylcholinesterase
Xg glycoprotein
Sc glycoprotein
Do glycoprotein
Channel-forming integral protein (CHIP)
LW glycoprotein
C4A glycoprotein
C4B glycoprotein
-2-L-fucosyltransferase
Kx glycoprotein
Glycophorin C and glycophorin D
CD55 (decay-accelerating factor)
CD35 (CR1)
CD44
CD147
Not defined

The phosphates that join the DNA nucleotides link the

5-carbon of one deoxyribose to the 3 carbon of the next
deoxyribose. For line drawings of single strands, the convention is to show the 5 end at the left and the 3 end at
the right. The complementary strands of double-stranded
DNA have opposite directionality. By convention, the top
strand reads from the 5 end to the 3 end, while its complementary strand appears below it with the 3 end on the left.

BLOOD GROUP ANTIGEN AND GENE TERMINOLOGY

peats (e.g., 1999(AT)4-16 denotes an AT

sequence beginning at nt 1999 [an A] and
repeated between 4 and 16 times in the
Blood group system
Traditional
ISBT
ISGN
population).
Rh
D, Rh29
RH1,RH29
RH*D, RH*29
Intron mutations: If the full geLutheran
Lua, Lub
LU1, LU2
LU*A, LU*B
Kell
K, k
KEL1, KEL2
KEL*1, KEL*2
nomic sequence is known, this can be
a
b
Duffy
Fy , Fy
FY1, FY2
DARC*A, DARC*B
used for numbering. As this genomic seKidd
Jka, Jkb
JK1, JK2
SLC14A1*A, SLC14A1*B
quence is often not known, the intron
Diego
Di a, Di b
DI1, DI2
SLC4A1*A, SLC4A1*B
Scianna
Sc1, Sc2
SC1, SC2
SC*1, SC*2
intervening sequence (IVS) numbers can be
used, with positive numbers commencing
Amino acids
with the G of the invariant donor splice site GT and
negative numbers starting from the G of the invariant
Proteins consist of 20 amino acids. Each amino acid is enacceptor splice site AG. The base intron can be desigcoded by one or more distinct codons in DNA (e.g., GCT,
nated by the intron number (e.g., IVS3) or by the cDNA
GCC, GCA, and GCG code for alanine). Table 11 lists the
nt number (designated with a c.) (i.e., the number of
symbols for the amino acids.
the last nt of the exon preceding the intron or the number of the first nt of the exon following that intron). For
Mutations
example, one mutation (of many) that leads to the Rhnull
A nomenclature for gene mutations has recently been pubphenotype is IVS6-lG>A, which can also be designated
lished44 and this is the terminology that TRANSFUSION will
c.946-1G>A, as nt 946 is the first nt of exon 7 of RHAG
use. This nomenclature for the common types of nucleotide
(Rh-associated glycoprotein gene).
changes and amino acid substitutions is described below,
Unique identifier: This can be obtained through
using examples from blood group genes; additional exhttp://www.ncbi.nlm.nih.gov/Omim/,
amples are listed in Table 12.
http://www.uwcm.ac.uk/uwcm/mg/hgmd0.html,
Nucleotides.
or a database curator. For additional useful Web sites,
Numbering: The A of the initiator methionine codon
see Table 13.
(ATG) is designated +1. If any ambiguity could arise
Amino acids.
(e.g., alternative initiation sites), a reference sequence
Numbering: Initation methionine is position 1. Single
from a database or an alternative explanation should
letter amino acid code is preferred (with X for a stop
be designated for numbering.
codon); the three letter code is also acceptable.
General format: The nucleotide (nt) number is listed
General format: The amino acid is listed first, followed
first, then the change (e.g., substitution, deletion, or inby the codon number and the mutation change. This
sertion) is given.
nomenclature prevents confusion concerning the
Substitutions: The k/K substitution in the KEL gene is
meaning of G, C, A, and T as amino acids or nts.
designated 578C>A, denoting a C at nt 578 in the k alSubstitutions: The amino acid of the wild-type protein
lele replaced by an A in the K allele.
is given first, followed by the amino acid number, and
Deletions: Designated by nt numbers followed by del
then the mutant (variant) amino acid. For example, the
and (optionally) the deleted sequence. Thus, the comk/K polymorphism is designated T193M.
mon A/O polymorphism is 261delG, denoting the deDeletions: G99del denotes deletion of codon 99 for glyletion of a G at nt 261 of the ABO gene. For deletions of
cine.
more than one nt, the format is 1999-2001delACT for
Insertions: G99-100ins denotes that glycine is inserted
a 3-nt deletion (ACT can be omitted).
between codons 99 and 100.
Insertions: Format is nt number(s) followed by "ins"
TABLE 8. Some examples of blood group allele terminology
Allele terminology

and the extra nts. For example, one variant of the Co(a
b) phenotype is 308-309insT, denoting the insertion
of a T between nts 308 and 309 of the AQP1 gene. In
cases of ambiguity in the location of insertions in short
repeats, the 3 nt is chosen (e.g., insertion of a C into
the sequence ACCCT would be denoted as an insertion
between the C and the T).
Variable short sequence repeats: Designated as the first
nt of the first repeat followed by the short repeat sequence (in parentheses) and then the number of re-

FINAL THOUGHTS
Using correct terminology is as important as using correct
English in writing and conversation. The correct form for
both is the most efficient method of communicating the
message clearly. Unfortunately, many investigators and
well-known medical journals are not attentive to correct
blood group antigen nomenclature and terminology. We

Volume 40, April 2000 TRANSFUSION 483

GARRATTY ET AL.

TABLE 9. Examples of terminology for serologic phenotypes [ISBT numerical terminology]

Blood group systems
ABO system
A
[ABO:1,2,3]
B
[ABO:1,2,3]
O
[ABO:1,2,3]
AB [ABO:1,2,3]
A1 [ABO:1,2,3,4]
A2 [ABO:1,2,3,4]
MNS system
M+ N+ S s+ U+ He Mi(a+)
[MNS:1,2,3,4,5,6,7]
Alternatively, Miltenberger41 or glycoprotein (GP)42 terminology, such as Mi.III or GP.Mur, can be used.
Null phenotypes:
Mk (MNSsU, etc.)
[MNS:1,2,3,4,5, etc.]
En(a) S+s+U+
[MNS:1,2,3,4,5]
M+N+U or SsU
[MNS:1,2,3,4,5]
P system
P1+ [P:1]
P1 [P:1]
P2 can only be used as an alternative to P1 when the cells have been shown to be P+.
Rh system
D+ C+ E c+ e+ Cw Rh:32,33,Be(a) (the order D C c E e would also be acceptable),[RH:1,2,3,4,5,8,32,33,36]
It is also acceptable to use probable genotypes as phenotypes, providing it is made clear that they are only probable genotypes based
on haplotype frequencies: e.g., R1R2 or DCe/DcE, R1r Cw+ or DCe/dce Cw+
Null and mod phenotypes:
Rhnull
[RH:1,2,3,4,5,29]
Rhmod
[RH: w1,w2,3,w4, etc.)
Lutheran system
Lu(ab+) Lu:3,4
[LU:1,2,3,4]
Null phenotype: Lunull or Lu(ab)
[LU:1,2,3]
Kell system
K k+ Kp(ab+c) Js(ab+) Ku+ K:11,12,13,17
[KEL:1,2,3,4,5,6,7,11,12,13,17,21]
Null and mod phenotypes:
K0 or Kellnull
[KEL:1,2,3,4,5]
Kmod
[KEL:1,w2,3,w4, etc.]
Lewis system
Le(ab+) Le(ab+)
[LE:1,2,3]
Le(ab) Le(ab)
[LE:1,2,3]
Duffy system
Fy(a+b+) Fy:3
[FY:1,2,3]
Fy(ab) Fy:3
[FY:1,2,3]
x
Fy may be used as a phenotype.
Kidd system
Jk(a+b) Jk:3
[JK:1,2,3]
Jk(ab) Jk:3
[JK:1,2,3]
Diego system
Di(a+b+) Wr(ab+) Wd(a) Rb(a) WARR [DI:1,2,3,4,5,6,7]
Yt system
Yt(a+b) [YT:1,2]
Xg system
Xg(a+)
[XG:1]
Scianna system
Sc:1,2,3 [SC:1,2,3]
Dombrock system
Do(a+b+) Gy(a+) Hy+ Jo(a+)
[DO:1,2,3,4,5]
Colton system
Co(a+b) Co:3
[CO:1,2,3]
Co(ab) Co:3
[CO:1,2,3]
Landsteiner-Wiener system
LW(a+b) LW(ab+)
[LW:5,6,7]
LW(ab) LW(ab)
[LW:5,6,7]
Chido/Rodgers system
Ch:1,2 WH Rg:1,2
[CH/RG:1,2,7,11,12]
Hh system
H+
[H:1]
H
[H:1]
The symbol Oh may be used for the true Bombay phenotype (RBCs totally H-deficient from nonsecretors). Otherwise the terms RBC
H-deficient secretor and RBC H-deficient nonsecretor are recommended.
Kx system
Kx+
[XK:1]
Kx or McLeod
[XK:1]
Table 9 continued on next page.

484 TRANSFUSION Volume 40, April 2000

BLOOD GROUP ANTIGEN AND GENE TERMINOLOGY

TABLE 9. (cont'd.)
Blood group systems (cont'd)
Gerbich system
Ge:2,3,4 Wb Ls(a) An(a) Dh(a)
[GE:2,3,4,5,6,7,8]
Gerbich phenotype may be used instead of Ge:2,3,4
[GE:2,3,4].
Yus phenotype may be used instead of Ge:2,3,4
[GE:2,3,4].
Leach phenotype may be used instead of Ge:2,3,4
[GE:2,3,4].
Cromer system
Cr(a+) Tc(a+bc) Dr(a+) Es(a+) IFC+ WES(ab+) UMC+
[CROM:1,2,3,4,5,6,7,8,9,10]
Null phenotype: Inab phenotype
[CROM:1,2,3,4,5,6,7,8,9,10]
Knops system
Kn(a+b) McC(a+) Sl(a+) Yk(a+) [KN:1,2,3,4,5]
Null phenotype: Helgeson phenotype
Indian system
In(ab+) [IN:1,2]
Ok system
Ok(a+)
[OK:1]
Ok(a)
[OK:1]
Raph system
MER2+ [RAPH:1]
Antigen collections
Cost collection
Cs(a+b) [COST:1,2]
Ii collection
I adult
i adult
i cord
The numerical designations for these phenotypes have not been provided, as they are to be modified in the near future.
Er collection
Er(a+b) [ER:1,2]
GLOB collection
p
P1k
P2k
LKE+
The numerical designations for these phenotypes have not been provided as they are to be modified in the near future.
Low-frequency antigen (700) series and high-frequency antigen (901) series
700 series
By, Chr(a), Bi, Bx(a)
[700:2,3,5,6]
901 series
Vel+, Lan+, At(a+), Jr(a+)
[901:1,2,3,5]

TABLE 11. Amino acid symbols

Amino acid

TABLE 10. Nucleosides and nucleotides

Base

Nucleoside

Nucleotide
abbreviation

Thymine
Cytosine
Adenine
Guanine

Thymidine
Cytidine
Adenosine
Guanosine

T
C
A
G

Molecular
class
Pyrimidine
Pyrimidine
Purine
Purine

Reprinted with permission from the American Medical Association

manual of style.43

hope that this review of current nomenclature will help

readers and other journals realize that proper nomenclature reminds us of the history of RBC antigen discovery,
indicates functional roles for RBC membrane proteins, and
provides consistent guidelines for communicating research
on RBC surface antigens.

Alanine
Arginine
Asparagine
Aspartic acid
Cysteine
Glutamine
Glutamic acid
Glycine
Histidine
Isoleucine
Leucine
Lysine
Methionine
Phenylalanine
Proline
Serine
Threonine
Tryptophan
Tyrosine
Valine

Three-letter
symbol

Single-letter
symbol

Ala
Arg
Asn
Asp
Cys
Gln
Glu
Gly
His
Ile
Leu
Lys
Met
Phe
Pro
Ser
Thr
Trp
Tyr
Val

A
R
N
D
C
Q
E
G
H
I
L
K
M
F
P
S
T
W
Y
V

Reprinted with permission from the American Medical Association

manual of style.43

Volume 40, April 2000 TRANSFUSION 485

GARRATTY ET AL.

TABLE 12. Some examples of blood group gene mutations

Example

Gene

k/K
RhE/Rhe
Fya/Fyb
Co(ab)*

KEL
RHCE
DARC
AQP1

Rhnull*

RHAG

RHCE

Nucleotide

Amino acid

578C>A
676C>G
131G>A
113C>T
308-309insT
836G>A
IVS1+1G>A
IVS61G>A
[966delT;968delA]

T193M
P226A
G44D
P38L
Frameshift
G279E
Prevents splicing
Skips exon 7
Frameshift

* There are several genetic mutations underlying the Co(ab) and Rhnull phenotypes; only
a few are listed here.

TABLE 13. Useful Web sites

Name of Web site (Sponsor)

Web site

American Association of Blood Banks

TRANSFUSION (American Association of Blood Banks)
Working Party on Blood Group Terminology (ISBT)
Serum, Cells and Rare Fluid Exchange (SCARF)
Amos WWW links page
Pedros Biomolecular Research Tools
National Institutes of Health
Guidelines for Human Gene Nomenclature
Albert Einstein College of Medicine

http://www.aabb.org
http://www.transfusion.org
http://www.iccbba.com/page25.htm
http://scarf.uth.tmc.edu/index.html
http://www.expasy.ch/alinks.html
http://www.public.iastate.edu/~pedro/research_tools.html
http://www.nhgri.nih.gov/DIR/VIP/Glossary/
http://www.gene.ucl.ac.uk/nomenclature/guidelines.html
http://www.bioc.aecom.yu.edu/bgmut/index.htm

REFERENCES
01. Landsteiner K. [Agglutination phenomena in normal human blood.] Wien Klin Wochenschr 1901;14:1132-4. [An
English translation, by A.L. Kappus, appears in Transfusion
1961;1:5-8.]
02. Von Decastello A, Sturli A. [Concerning isoagglutinins in
serum of healthy and sick humans.] Munch Med
Wochenschr 1902;26:1090-5. [An English translation appears in Selected Contributions to the Literature of Blood
Groups and Immunology, vol 1. Landsteiner Centennial,
Fort Knox, KY: Blood Transfusion Division, US Army Medical Research Laboratory, 1966: pp 19-38.]
03. Landsteiner K. [Specific binding and antibodies. IV. hemagglutination and hemolysis.] In: Oppenheimer C, ed.
Handbuch der Biochemie des Menschen und der Tiere, vol
2, part 1. Jena: Gustav Fischer Verlag, 1910:395-541. [An English translation can be found in Selected Contributions to
the Literature of Blood Groups and Immunology, vol 5.
Landsteiner Centennial. Fort Knox, KY: Blood Transfusion
Division, US Army Medical Research Laboratory, 1968:106331.
04. Von Dungern E, Hirszfeld L. [Concerning the group-specific
structures of the blood.] Z Immunitatsforsch Exp Ther
1911;8:526-62. [An English translation can be found in Selected Contributions to the Literature of Blood Groups and
Immunology, vol 1. Landsteiner Centennial. Fort Knox, KY:
Blood Transfusion Division, US Army Medical Research
Laboratory, 1966:39-81.]

486 TRANSFUSION Volume 40, April 2000

05. Daniels GL, Anstee DJ, Cartron JP, et al. Terminology for red
cell surface antigens. ISBT Working Party Oslo Report. International Society of Blood Transfusion. Vox Sang 1999;77:52-7.
06. Jansky J. Haematologick studie u. psychotiku. Sb Klin
1907;8:85-139.
07. Moss WL. Studies on isoagglutinins and isohemolysins.
Bull Johns Hopkins Hosp 1910;21:63-70.
08. Isohemagglutination. Recommendation that the Jansky classification be adopted for universal use. JAMA 1921;76:130.
09. Landsteiner K. Current comments. JAMA 1927;88:421-2.
10. Kennedy JA. Blood group classifications used in hospitals in
the United States and Canada. JAMA 1929;92:610-5.
11. Landsteiner K, Wiener AS. An aggutinable factor in human
blood recognised by immune sera for rhesus blood. Proc
Soc Exp Biol Med 1940;43:223-4.
12. Fisher RA, Race RR. Rh gene frequencies in Britain. Nature
1946;157:48-9.
13. Race RR, Sanger R. Blood groups in man. Oxford: Blackwell,
1950.
14. Wiener AS. Karl Landsteiner, M.D. History of Rh-Hr blood
group system. NY State J Med 1969;69:2915-35.
15. Mazumdar PM. Species and specificity. Cambridge: Cambridge University Press, 1995:337-78.
16. Andresen PH, Callender ST, Fisher RA, et al. A notation for
the Lewis and Lutheran blood-group systems (letter). Nature 1949;163:580.
17. Issitt PD, Anstee DJ. Applied blood group serology. 4th ed.
Durham, NC: Montgomery Scientific, 1998.
18. Allen FH, Diamond LK, Niedziela B. A new blood-group antigen (letter). Nature 1951;167:482.

BLOOD GROUP ANTIGEN AND GENE TERMINOLOGY

19. Levine P. A review of Landsteiners contributions to human

blood groups. Transfusion 1961;1:45-52.
20. Wiener AS, Unger LJ, Cohen L, et al. Type-specific cold
auto-antibodies as a cause of acquired hemolytic anemia
and hemolytic transfusion reactions: biologic test with bovine red cells. Ann Intern Med 1956;44:221-40.
21. Morgan WT, Watkins MM. The detection of a product of the
blood group O gene and the relationship of the so-called Osubstance to the agglutinogens A and B. Br J Exp Pathol
1948;29:159-73.
22. Wiener AS, Unger LJ, Gordon EB. Fatal hemolytic transfusion reaction caused by sensitization to a new blood factor
U. JAMA 1953;153:1444-6.
23. Darnborough J, Dunsford I, Wallace JA. The Ena antigen

24.

25.

26.
27.

28.
29.

30.
31.

32.
33.

34.
35.

36.
37.

and antibody. A genetical modification of human red cells

affecting their blood grouping reactions. Vox Sang
1969;17:241-55.
Bizot M, Lomas C, Rubio F, Tippett P. An antiserum identifying a red cell determinant expressed by Rh:33 and by some
new depressed Rh phenotypes. Transfusion 1988;28:342-5.
Lomas C, Grssmann W, Ford D, et al. FPTT is a low-incidence Rh antigen associated with a new partial Rh D phenotype, DFR. Transfusion 1994;34:612-6.
Prokop O, Uhlenbruck G. Human blood and serum groups.
New York: Wiley Interscience, 1969:103.
Cartron JP, Rouger P. Blood cell biochemistry, Vol 6. Molecular basis of human blood group antigens. New York:
Plenum Press, 1995:433.
Roelcke D, Uhlenbruck G. Antigen nomenclature. Vox Sang
1970;18:478-9.
Booth PB, Jenkins WJ, Marsh WL. Anti-IT: A new antibody of
the I-blood-group system occurring in certain Melanesian
sera. Br J Haematol 1966;12:341-4.
Allen FH Jr, Rosenfield RE. Notation for the Kell bloodgroup system. Transfusion 1961;1:305-7.
Rosenfield RE, Allen FH Jr, Swisher SN, Kochwa S. A review
of Rh serology and presentation of a new terminology.
Transfusion 1962;2:287-312.
Reid ME, Lomas-Francis C. The blood group antigen
factsbook. New York: Academic Press, 1997.
Allen FH Jr, Anstee DJ, Bird GWG, et al. ISBT Working Party
on Terminology for Red Cell Surface Antigens. Vox Sang
1982:42:164-5.
Lewis M, Anstee DJ, Bird GW, et al. Blood group terminology 1990. Vox Sang 1990;58:152-69.
Daniels GL, Anstee DJ, Cartron JP, et al. Blood group terminology 1995. ISBT Working Party on Terminology for Red
Cell Surface Antigens. Vox Sang 1995;69:265-79.
Issitt PD, Crookston MC. Blood group terminology: current
conventions. Transfusion 1984;24:2-7.
Issitt PD, Moulds JJ. Blood group terminology suitable for
use in electronic data processing equipment. Transfusion
1992;32:677-82.

38. Shows TB, McAlpine PJ, Boucheix C, et al. Guidelines for

human gene nomenclature. An international system for
human gene nomenclature (ISGN, 1987). Cytogenet Cell
Genet 1987;46:11-28.
39. Shows TB, McAlpine PJ, Boucheix C, et al. Guidelines for
human gene nomenclature: an international system for human gene nomenclature (ISGN 1989). Cytogenet Cell Genet
1987;46:11-28.
40. White JA, McAlpine PJ, Antonarakis S, et al. Guidelines for
human gene nomenclature (1997). HUGO Nomenclature
Committee. Genomics 1997;45:468-71.
41. Dahr W. Miltenberger subsystem of the MNSs blood group
system. Review and outlook. Vox Sang 1992;62:129-35.
42. Tippett P, Reid ME, Poole J, et al. The Miltenberger subsystem: is it obsolescent? Transfus Med Rev 1992;6:170-82.
43. American Medical Association manual of style. A guide for
authors and editors. 9th ed. Philadelphia: Williams &
Wilkins, 1998:366-92.
44. Antonarakis SE. Recommendations for a nomenclature system for human gene mutations. Nomenclature Working
Group. Hum Mutat 1998;11:1-3.

APPENDIX 1.
COMMONLY USED MOLECULAR
BIOLOGIC TERMS
Allele-specific oligonucleotide PCR (ASOPs), sequencespecific primer PCR: Method by which allele specific primers (approx. 20 bp) are used for PCR amplification. Hybridization may be disrupted by a mismatch of a single
nucleotide, and therefore failure to amplify may signify a
mutation or polymorphism in the gene.
Amplicon or replicon: Specific points at which DNA replication is initiated. A molecule of DNA has multiple replicons.
Annealing: Process by which complementary antiparallel
segments of DNA pair, creating a DNA duplex.
Arbitrarily primed PCR (genomic fingerprinting technique): Use of an undefined primer to amplify unknown
segments of the DNA.
Codon: A set of three nts that code for one amino acid or
chain termination.
cDNA: Double-stranded DNA that represents expressed sequences of the genome, obtained by the reverse transcription of mRNA.
Conserved regions: Certain regions of DNA are highly conserved, within and across species. Such regions are most
common in expressed sequences that tolerate little variability and in functional gene sequences, such as splice sites
and initiation sequences.
Conserved 5 UTR (untranslated region): Sequence downstream of transcription start and upstream of translation
start.

Volume 40, April 2000 TRANSFUSION 487

GARRATTY ET AL.

Denaturation: Process by which the hydrogen bonds between bps are broken to create two single-stranded antiparallel and complementary strands of DNA.
Downstream: To the right of a sequence, read from 5 to 3,
or from left to right.
End labeling: Incorporation of 32P at the 5 end of an oligonucleotide via polynucleotide kinase and gamma-labeled
ATP.
Elongation: Polymerization of nts to create nucleic acid
molecules. Elongation proceeds 5 to 3 via a condensation
reaction.
Exon: Segment of a gene that is expressed. It is present only
in eukaryotes.
Forward or sense primer: The forward or sense primer anneals to the 3 end of the anti-sense strand and primes the
synthesis of the sense strand.
Gene: A DNA segment that contributes to phenotype or
function. In the absence of demonstrated function, a gene
may be characterized by sequence, transcription, or homology.
Gene conversion: Nonreciprocal exchange of genetic information as a result of heteroduplex formation between nonsister chromatids. Mismatches in the region of the heteroduplex are corrected so that one strand acts as the acceptor,
which is made to complement the second strand, the donor (i.e., base changes occur on one strand only, the acceptor strand). Disruption of the duplex and subsequent DNA
synthesis therefore create a portion of the acceptor strand,
the length of the heteroduplex, that mirrors the sequence
of the donor strand. Heteroduplex formation between allele pairs results in allelic conversion, while heteroduplex
formation between nonallelic pairs, due to a high degree of
homology, results in interlocus conversion.
Gene transduction: Transfer of genetic material (i.e., genes)
using a virus as the vector.
Genomic DNA: The entire genome of an organism that includes nuclear and extranuclear DNA (i.e., mitochondrial
DNA).
Haplotype: A series of linked alleles within a defined region
on a single maternal or paternal chromosome.
Homology: Segments of DNA from a variety of organisms
may display sequence similarity, or homology. The amount
of homology between species may be used to determine
evolutionary relationships and degrees of divergence. Functional genes often display homology across species; for example, homeobox genes that control early development
show high degrees of homology across species.
Hot-start PCR: Method of PCR in which the enzyme used
for the amplification reaction (i.e., Taq polymerase) is added
to template DNA that has been heated to 95C.
Hybridization: The annealing of single-stranded nucleic
acid chains.
Hypervariable region or hypervariable minisatellite DNA:
Highly polymorphic arrays of tandemly repeated DNA se-

488 TRANSFUSION Volume 40, April 2000

quences (0.1-20 kb). Most are found near the telomere and
are not transcribed.
Intron: The intervening stretches of DNA between exons.
They are spliced out of the gene at the RNA level and are
not expressed as part of the gene product (protein).
Microsatellite: Small array of simple tandem repeats, usually 1 to 4 bp in length.
mRNA: Messenger RNA. DNA is transcribed into RNA,
which is eventually translated into protein.
Mutation: An error or permanent alteration that has occurred in the coding sequence of a gene or genetic regulatory element. There are several classes of mutations (nonsense, frameshift, insertion, deletion, and point mutation).
Northern blot/Southern blot: Hybridization techniques in
which single-stranded target nucleic acids, separated by
length by gel electrophoresis, are transferred and fixed to
nitrocellulose or nylon membranes. Radiolabeled probes
are used to demonstrate the presence or absence of target
nucleic acid sequences. In a Southern blot, the target is
DNA. In a Northern blot, the target is RNA.
NCRs (noncoding regions) of the genome: Segments of the
genome that are not expressed. Extensive regions of noncoding DNA are found at the teleomeres and around the
centromere, often termed heterochromatic DNA. NCRs are
also found within genes (e.g., introns and 5 and 3 UTRs).
Nucleoside: A nucleotide without a phosphate group.
Nucleotide: Building blocks of DNA and RNA. Composed
of phosphate groups, a 5-sided sugar molecule (ribose in
RNA; deoxyribose in DNA), and nitrogen-containing bases.
Nucleotide substitutions: Nucleotide substitutions are of
two types: 1) transitions, purine to purine or pyrimidine to
pyrimidine; and 2) transversions, purine to pyrimidine and
pyrimidine to purine. Naturally occurring substitutions
may occur via tautomerization of nucleotides. Nucleotide
analogues may also cause substitutions.
Oligonucleotide: Short polymer of nucleic acids. Often
made in vitro for use as probes.
Palindromes: Short sequences of DNA that may be read the
same in the forward and reverse direction: for example,
ATATTAATAT on one DNA strand and TATAATTATA on the
complementary strand. Palindromes may assume a specific
secondary structure that facilitates recognition.
PCR: In vitro method for the amplification of a specific sequence of DNA, using sequence-specific primer sets. The
temperature of the reaction is controlled such that amplification occurs in cycles.
Phage: A virus of bacteria, phage such as lambda have been
used to introduce foreign DNA into bacteria.
Plasmid: Nonessential, circular, supercoiled DNA that is
found in bacteria. Copy number is high, and the plasmid
replicates autonomously.
Primers: Short nucleic acid sequences, oligonucleotides,
that bind specifically to single-stranded target DNA. The 3

BLOOD GROUP ANTIGEN AND GENE TERMINOLOGY

end (hydroxy group) of the primer allows for elongation of

the primer and therefore DNA synthesis. Primers are synthesized in vitro.
Probe: A labeled oligonucleotide that serves to detect specific sequences via heteroduplex formation.
Recombinant proteins: Proteins produced by the expression of a gene, modified or unmodified, that is engineered
into an appropriate vector system (i.e., SV40 expression
vector). For example, recombinant EPO may be produced
by the insertion of the EPO gene into an expression vector,
that may then be introduced into mammalian cells which
serve to house the production of the recombinant proteins.
Restriction enzymes or endonucleases: Enzymes that recognize and cleave specific sequences of double-stranded
DNA. For cleavage to occur, sites may require methylation.
Reverse or anti-sense primer: The reverse or anti-sense
primer anneals to the 3 end of the sense strand and primes
the synthesis of the anti-sense strand.
Reverse transcription: Method by which single-stranded
RNA (i.e., cDNA) is converted to double-stranded DNA. Reverse transcriptase is required.
Restriction fragment length polymorphism (RFLP) fragments: Obtained by the digestion of DNA with a particular
restriction enzyme. Fragment lengths are dependent on the
location and frequency of restriction sites, which may vary
from one individual to the next because of natural variability or mutations in DNA sequence.
rRNA: Ribosomal RNA is not translated, but collaborates
with ribosomal proteins to make ribosomes. Three distinct
species of rRNA exist in eukaryotes28S, 18S, and 5.8S rRNA
where S is a measure of the sedimentation coefficient.
Reverse transcription-PCR: Ideal for the amplification of
expressed sequences. The cDNA, isolated by reverse transcription of mRNA, acts as the template. Exon-specific
primers are used to start the reaction.

Splicing: Removal of introns and subsequent rejoining of

exons in the mature mRNA molecule.
Stringency: Heteroduplex formation between probes and
target DNA is accomplished by controlling the environment
in which hybridization occurs. Mismatches may be tolerated in solutions of high salt concentration and low temperature or low stringency, because salts stabilize the association of DNA by minimizing electrostatic repulsion of the
negatively charged DNA backbone. Low temperatures prevent melting of DNA or disruption of hydrogen bonding.
Therefore, stringency is a measure of the specificity of heteroduplex formation. High stringency equates to increased
specificity.
Synthetic oligonucleotide probes: Probes that are made in
vitro.
Transcripts: Single-stranded RNA copies of DNA that run
5 to 3.
Transfer RNA (tRNA): RNA that assumes a cloverleaf structure and facilitates protein synthesis. The tRNA binds specifically to mRNA codons via an anticodon and interacts
with ribosomes and rRNA. Transfer of an amino acid to the
3 end of the tRNA is specified by the anticodon.
Upstream: To the left of a sequence, read from 5 to 3, or
from left to right.
VNTR (variable number of tandem repeats): Alleles may
differ because of variability in the number of tandem repeats. VNTR polymorphism is observed by digesting DNA
with restriction enzymes specific for sequences flanking a
specific VNTR locus. Fragment length corresponds to the
number of repeats. A repeat unit is typically 5 to 64 bp in size.
Vector: An extrachromosomal genetic element that, when
incorporated into a recombinant DNA molecule, can cause
transfer of the DNA into a host cell.
Wild-type: A gene as it exists in nature.

Volume 40, April 2000 TRANSFUSION 489