Transfusion Medicine Reviews 30 (2016) 197–201

Contents lists available at ScienceDirect

Transfusion Medicine Reviews

journal homepage: www.tmreviews.com

Pediatric Section

Red Blood Cell Antigen Genotyping for Sickle Cell Disease, Thalassemia,
and Other Transfusion Complications
Ross M. Fasano a,⁎, Stella T. Chou b
a
Transfusion, Tissue, & Apheresis, Children's Healthcare of Atlanta, Departments of Clinical Pathology & Pediatric Hematology, Emory University School of Medicine, Atlanta, GA
b
Department of Pediatrics, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA

a r t i c l e i n f o a b s t r a c t

Available online 28 May 2016 Since the discovery of the ABO blood group in the early 20th century, more than 300 blood group antigens have
been categorized among 35 blood group systems. The molecular basis for most blood group antigens has been
Keywords: determined and demonstrates tremendous genetic diversity, particularly in the ABO and Rh systems. Several
Red blood cell antigen genotyping blood group genotyping assays have been developed, and 1 platform has been approved by the Food and Drug
Sickle cell disease Administration as a “test of record,” such that no phenotype confirmation with antisera is required. DNA-based
Thalassemia
red blood cell (RBC) phenotyping can overcome certain limitations of hemagglutination assays and is beneficial
Autoimmune hemolytic anemia
Alloimmunization
in many transfusion settings. Genotyping can be used to determine RBC antigen phenotypes in patients recently
Rh transfused or with interfering allo- or autoantibodies, to resolve discrepant serologic typing, and/or when typing
antisera are not readily available. Molecular RBC antigen typing can facilitate complex antibody evaluations and
guide RBC selection for patients with sickle cell disease (SCD), thalassemia, and autoimmune hemolytic anemia.
High-resolution RH genotyping can identify variant RHD and RHCE in patients with SCD, which have been associ-
ated with alloimmunization. In the future, broader access to cost-efficient, high-resolution RBC genotyping tech-
nology for both patient and donor populations may be transformative for the field of transfusion medicine.
© 2016 Published by Elsevier Inc.

Contents

Challenges in Transfusion Management of SCD, Thalassemia, and Those With Warm Autoantibodies . . . . . . . . . . . . . . . . . . . . . . . . 198
Molecular Background of Blood Group Antigen Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198
Red Blood Cell Genotyping Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
Indications for RBC Genotyping . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
Recent or Chronic Transfusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
Sickle Cell Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
Thalassemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200
Autoimmune Hemolytic Anemia and Warm Autoantibodies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200
Blood Donors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200
Summary/Research Priorities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200
Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201

Genetic characterization of blood group antigens has demonstrated

⁎ Corresponding author at: Ross M. Fasano, MD, Transfusion, Tissue, & Apheresis,
Children's Healthcare of Atlanta, Departments of Clinical Pathology & Pediatric Hematology,
Emory University School of Medicine, 7105B Woodruff Memorial Building, 101 Woodruff
Circle, Atlanta, GA, 30322.
E-mail addresses: Ross.fasano@emory.edu (R.M. Fasano), chous@email.chop.edu
(S.T. Chou).
significant diversity among populations. Genomic data are increasingly
incorporated into standard clinical care, and molecular methods to
predict red blood cell (RBC) antigen phenotypes have improved our
approach to transfusion practice. Hemagglutination using RBCs and
blood group antigen-specific antisera is a simple and robust method for
RBC antigen typing of blood donors and patients, but has some limitations
for which DNA-based testing provides an alternative. These include

http://dx.doi.org/10.1016/j.tmrv.2016.05.011
0887-7963/© 2016 Published by Elsevier Inc.
198 R.M. Fasano, S.T. Chou / Transfusion Medicine Reviews 30 (2016) 197–201

extended RBC phenotype determination in patients recently transfused or
with interfering allo- or autoantibodies, discrepant serologic typing
results and/or when typing antisera are not readily available, paternal
RhD zygosity testing for pregnancies at risk for RhD hemolytic disease
of the fetus and newborn (HDFN), and prenatal determination of fetal
blood group antigen status in allosensitized mothers at risk of HDFN
(Table) [1]. Red blood cell genotyping is also an efficient method for
donor centers to identify RBC units with rare or uncommon antigen
phenotypes, or simply to meet demands for antigen-negative units
(Table) [2]. In particular, maintenance of large pools of African American
blood donors with extended RBC antigen characterization is needed to
support patients with sickle cell disease (SCD). Although identification
of these donor units has historically been done serologically, automated
DNA-based antigen testing can potentially improve the efficiency,
reliability, and extent of matching for this heavily transfused population.
Challenges in Transfusion Management of SCD, Thalassemia, and
Those With Warm Autoantibodies
Transfusion therapy is a key component of the comprehensive
management of patients with SCD and thalassemia [3]. Current clinical
guidelines recommend RBC transfusion for patients with SCD to treat
acute complications including acute chest syndrome, stroke, aplastic
crisis, and splenic sequestration, and before surgical procedures involving
general anesthesia [4]. Primary and secondary stroke prevention is the
major indication for chronic RBC transfusion therapy, with approximately
10% of children with SCD requiring regular transfusions [5]. Chronic
transfusions are used to reduce ineffective erythropoiesis for patients
with severe thalassemia (β thalassemia major) and are used intermit-
tently for patients with milder forms of thalassemia [6].
Transfusion therapy for patients with SCD and thalassemia is
complicated by high rates of alloimmunization. The prevalence of
alloimmunization with ABO/Rh(D) matching alone ranges from 18% to
Table
Indications for RBC antigen genotyping
75% and from 4% to 37% in patients with SCD and thalassemia respectively
[3,7]. The wide range of prevalence results from differences in
exposure frequency, patient age (pediatric vs adult), and donor/recipient
RBC antigen discordance. Alloantibodies to Rh (primarily C and E) and K
comprise over two thirds of antibodies detected. In an effort to reduce
RBC alloimmunization, many transfusion services have implemented
prophylactic phenotype matching for C, E, and K antigens for patients
with SCD and thalassemia. For SCD, this transfusion strategy has been
associated with a reduction in alloimmunization prevalence from
18% to 75% (rate: 1.7 to 3.9 antibodies/100 U transfused) with ABO/
Rh(D) matching only, to 5% to 24% (0.26 to 0.50 antibodies/100 U trans-
fused) with C-, E-, and K-matched RBCs, and further reduced to 0% to
7% (≤0.10 antibodies/100 U transfused) with extended antigen matching
(beyond C, E, and K) [8].
Despite receiving Rh phenotype–matched RBCs, many patients with
SCD form Rh antibodies that may appear like autoantibodies since the
patient's own RBCs type positive for the corresponding Rh antigen
with standard serologic tests. RBC genotyping for RHD and RHCE has
revealed that many of these patients carry variant alleles that encode
partial D, C, and/or e antigens, and suggests that these were alloanti-
bodies directed toward common Rh epitopes the patient lacks. Many
of these Rh antibodies have been associated with laboratory evidence
of delayed hemolytic transfusion reactions or demonstrated decreased
survival of transfused RBCs [9,10]. Anti-D has also been reported
in D+ patients with thalassemia, but it is unknown whether these
patients had variant RH genotypes that could predispose them to D
immunization [11].
Transfusion management of children with autoimmune hemolytic
anemia or warm autoantibodies present additional challenges. In most
cases, autoantibodies interfere with standard pretransfusion antibody
screening and compatibility testing. This is most problematic if the
child has been previously transfused and underlying alloantibodies
have formed [12]. Time- and resource-consuming absorption tech-
niques primarily available at reference laboratories are required for
alloantibody evaluation and may not be effective in cases of high titer
or tightly bound autoantibodies.

Clinical indication Examples Molecular Background of Blood Group Antigen Systems

Patient typing
Recently or multitransfused Hemoglobinopathies (SCD, thalassemia
major/intermedia)
Congenital or acquired hemolytic anemias
Presence of interfering antibodies Autoantibodies, multiple alloantibodies,
antibodies to high-prevalence antigens,
antibody of undetermined specificity
Suspected antibody against antigens for Doa/b, Jsa/b, Kpa/b, V/VS
which typing antisera are not readily RBC antigen variants
available
Serologic typing discrepancy RhD typing discrepancy (due weak D,
partial D)
To detect silencing genes or genes To detect the GATA site mutation in the
responsible of a weakly expressed DARC gene in individuals who are Fy(b-)
antigen
Apparent autoantibody with Identify Rh variants (eg, anti-C, -e, or -D
antigenic specificity or unexplained in patients typing C+, e+, or D+)
antibodies despite antigen matching
To identify fetal risk for HDFN Paternal RhD zygosity testing
Determining weak D status in pregnant
females
Prenatal fetal blood group antigen
determination in allosensitized mothers
Blood donor typing
To screen for antigen-negative and/or Screening for rare combinations of
rare donors antigen-negative RBCs
Screening for RH genotype matched RBCs
for SCD patients with anti-Rh antibodiesa
To detect silencing genes Screening for ethnic African blood donors
by Fy(a-b-) phenotypea
a
Large-scale donor molecular screening for RH variant phenotypes in African blood
donors (established by Fy[a-b-] phenotype) has been reported to meet the transfusion
needs of patients with SCD and anti-Rh antibodies [37].
More than 300 blood group antigens in 35 blood group systems
exist, and the molecular basis for almost all blood group antigens and
phenotypes is known. DNA-based prediction of a blood group antigen
is simple and reliable for most antigens because most result from single
nucleotide polymorphisms (SNPs). Molecular assay design and inter-
pretation are thus straightforward for the prediction of most RBC anti-
gen phenotypes, which are determined by a limited number of alleles
or SNPs. However, DNA-based prediction of some blood group systems
remains challenging, most notably the ABO and Rh systems due to the
high number of variant alleles and their genetic complexity. In the
ABO system, more than 100 alleles encode the glycosyltransferases
responsible for the ABO type, and a single nucleotide change in an A
or B allele can result in an inactive transferase and a group O phenotype.
Mistyping of ABO antigens could lead to transfusion of ABO-
incompatible blood and a subsequent severe hemolytic transfusion
reaction. Genotyping methods have been developed to decrease the
risk for erroneous ABO prediction [13] but are unlikely to replace ABO
typing by hemagglutination, which is extremely reliable, inexpensive,
and has a quick turnaround time.
In the Rh system, molecular testing for the common Rh antigens D, C,
c, E, and e is uncomplicated for most populations. The RHD and
RHCE genes are each composed of 10 exons in opposite orientation
and share 97% nucleotide sequence homology. Their close proximity,
sequence homology, and opposite orientation have resulted in many
variant and hybrid alleles evolving on both loci [14]. Over 200 RHD
alleles encoding partial and weak D, and approximately 100 RHCE
alleles encoding altered or partial Rh antigens have been described.
 R.M. Fasano, S.T. Chou / Transfusion Medicine Reviews 30 (2016) 197–201
Patients with partial Rh antigens who lack certain Rh epitopes are at risk
of Rh alloimmunization. These same individuals may also lack high-
prevalence Rh antigens such as hrB or hrS, and alloantibodies to these
antigens can be difficult to identify. Conversely, variant RH alleles may
encode new Rh antigens (eg, V, VS, Go a) that are not routinely typed
for but are potentially immunogenic. RH variation is frequent in indi-
viduals of African descent, and nearly 90% of patients with SCD of
African descent carry at least one altered allele compared with 1% of in-
dividuals with European background. Variant RH alleles in patients with
SCD have been associated with persistently high alloimmunization
rates to Rh antigens despite C-, E-, and K-phenotype matched RBCs
from minority donors [9]. An additional complicating factor is that
altered RHCE and RHD encoding partial Rh antigens are often co-
inherited. Once alloimmunized, these patients pose significant challenges
to transfusion services in providing compatible RBCs in the absence of
access to RH genotyped donors.
Red Blood Cell Genotyping Methods
Many methods for RBC genotyping exist and vary in their complexity.
Several semiautomated platforms exist for testing common RBC anti-
gens, but evaluation for variants typically requires manual polymerase
chain reaction (PCR)–based assays, such as allele-specific primer PCR
or restriction fragment length polymorphism. Prototype RHD and RHCE
platforms to test for multiple RH variants have been developed, but
each of these target many, but not all, known alleles.
Most currently available semiautomated RBC molecular typing
platforms are DNA-based assays that use multiplex PCR amplification
of multiple genes encoding various blood group antigens, hybridization
to RBC antigen allele-specific oligonucleotide probes embedded on
either glass slides colored silica beads or fluidic bead suspensions, and
detection of fluorescence signals to predict a RBC phenotype [15–17].
At present, only one platform (PreciseType HEA; Immucor, Norcross,
Georgia) is approved in the United States for both patient and donor
typing by the Food and Drug Administration. Approved as a “test of
record,” no confirmatory typing with antisera is required, which is likely
to save time, reduce costs, and provide additional phenotype data that
are clinically relevant [18]. PreciseType HEA detects 24 polymorphisms
for the prediction of 38 RBC antigens including Rh (C/c, E/e, V, VS), Kell
(K/k, Js a/Js b, Kp a/Kp b), Duffy (Fy a/Fy b, Fy bweak, Fy bnull), Kidd (Jka/Jk b),
MNS (M/N, S/s, U), Lutheran (Lu a/Lu b), Dombrock (Doa/Do b, Hy, Joa),
Landsteiner-Wiener (LW a/LW b), Diego (Di a/Di b), Coltan (Co a/Co b),
and Scianna (Sc a/Scb) blood group systems. It also includes the hemo-
globin S mutation in the β-globin gene; however, this is not intended
or approved as a diagnostic test for SCD. Validation studies performed
in four U.S. laboratories demonstrated a greater than 99.4% agreement
to serology and 99.8% concordance with DNA sequencing [19,20].
Another commercially available high-throughput RBC molecular
typing assay is the BLOODchip ID CORE XT (Progenika Biopharma,
Biscay, Spain), which has been CE-marked in the European Union for
molecular typing of ABO (33 haplotypes), RHD (91 haplotypes including
many alleles which result in D-negative, partial D, weak D, and Del
phenotypes), RHCE (9 alleles), KEL (8 alleles), JK (4 alleles, including
2 JKnull), FY (4 alleles), MNS (9 haplotypes), DI, DO, and CO. This platform
demonstrated a global accuracy of 99.8% when compared with
serology and other molecular typing methods, with the exception
of ABO [17,21]. Other high-throughput RBC genotyping assays and
customizable platforms available include Luminex xMAP, GenomeLab
SNPstream (Beckman Coulter, Fullerton, California), and TaqMan
Open Array (Applied Biosystems, Grand Island, New York) [15].
Recently, Matrix-assisted laser desorption/ionization-time of flight
mass spectrometry–based blood group genotyping showed greater
than 99.2% concordance with serologic typing and proved useful in
identifying blood donors with rare phenotypes in the Kell, Kidd, and
Duffy systems [22].
199
The major limitation to current molecular platforms is their restric-
tion to detect known SNPs. Novel mutations, large deletions, hybrid al-
leles, and complex genes such as ABO and RH pose challenges for
current array-based platforms that are primarily designed to detect
SNPs and cannot accommodate every known variant. Target enrichment
next-generation sequencing alleviates some of these limitations by
providing comprehensive sequence information focused on specified
genomic regions. Target enrichment next-generation sequencing can
detect both established and novel SNPs, insertions and deletions, and
structural variations, and should be feasible for blood group typing as
the assay cost and ease of data interpretation improves [15,16]. Next-
generation sequencing is capable of sequencing the whole genome
(WGS) but is neither cost-efficient nor practical for application in clinical
transfusion medicine. However, as WGS is increasingly performed on
certain patients with chronic disease, blood group antigen phenotypes
including variants can be predicted [23]. Although rare, all PCR-based
techniques can fail to amplify alleles due to mutations in primer binding
sites (allele dropout), or conversely, amplify pseudogenes, both resulting
in false results.
Indications for RBC Genotyping
Recent or Chronic Transfusion
For recently transfused patients for whom an extended RBC pheno-
type is indicated, DNA-based assays are a reliable method to predict RBC
antigen status. Individuals who receive chronic transfusion therapy may
also benefit from RBC genotyping to establish their extended antigen
profile (N30 antigens) including those for which antisera are not
commercially available. This is especially helpful when patients develop
serologic reactivity that complicates alloantibody evaluation such as
autoantibodies, multiple alloantibodies, antibodies to high-prevalence
antigens, or antibodies against antigens for which typing antisera are
not readily available (eg, Doa/ b, Jsa/ b, Kpa/ b, V/VS) [1,18,24]. Currently,
there is 1 Food and Drug Administration-approved array for molecular
typing as a test of record [19].
Sickle Cell Disease
The National Heart, Lung, and Blood Institute recommends extended
RBC antigen typing for patients with SCD aged more than 6 months and
transfusion with prophylactic C-, E-, and K-matched RBCs [25]. Most
institutions obtain extended RBC phenotypes on patients with SCD
within the first year of life using serologic techniques. DNA-based RBC
typing has been implemented as the primary method for extended
RBC typing for patients with SCD at both of the authors' institutions
[18] and is feasible on buccal swab specimens in infants and young
children with SCD [26]. An additional benefit is the ability to detect the
GATA site mutation in the DARC gene, which is common in individuals
of African descent. This mutation prevents expression of Duffy glycopro-
tein on erythrocytes only while permitting expression in nonerythroid
cells. Individuals with this mutation are not at risk for alloimmunization
against Fyb despite typing as Fy(b−) and can receive Fy(b+) RBCs,
allowing for the preservation of Fy(b−) units [27,28].
RH variants are found frequently in individuals of African descent
whose RBCs express partial D, C, and e and may lack common Rh
epitopes (hrB, hrS) or be express new antigens (V, VS, Go a) (Figure)
[29]. Patients with SCD may form an alloantibody to the Rh epitope
they lack, but appear to have formed an autoantibody since their sero-
logic typing for that antigen is positive. High-resolution RH genotyping
can distinguish a potential alloantibody from an apparent autoantibody.
Thus, when unexplained Rh antibodies are detected in patients despite
Rh antigen matching, an evaluation for RH variants by genotype is
recommended. In addition, patients who develop antibodies to high-
prevalence Rh antigens often have the same panagglutination pattern
as autoantibodies. RH genotyping can identify individuals who lack
200 R.M. Fasano, S.T. Chou / Transfusion Medicine Reviews 30 (2016) 197–201
Figure. RH variants encoding partial Rh antigens, new Rh antigens, or lacking high-prevalence antigens. Examples of RHD and RHCE*ce variant alleles found in individuals of African
descent that encode partial D, C, c, and e antigens. RH variant alleles often result in a lack of high-prevalence antigens, including hrB, hrS, CEAG, and CELO or encode new antigens including
DAK, Go(a), V, VS, and RH43 [29].
high-prevalence Rh antigens such as hrB and hrS and facilitate antibody
evaluation and donor selection.
Although currently limited by cost and donor availability, use of
patient RH genotype information can improve donor RBC selection to
minimize Rh alloimmunization. A frequent variant allele in patients
with SCD is the hybrid RHD*DIIIa-CE(4–7)-D gene that encodes a partial
C antigen and does not encode D antigen [30]. Red blood cells are phe-
notypically C+, but individuals are at risk for anti-C if exposed to C
antigen encoded by a conventional allele. Patients with this allele and
who lack conventional RHCE*Ce should receive C− RBCs, consistent
with a prophylactic C matching policy [8]. For patients whose RH
genotypes predict exclusive expression of partial D and/or e antigens,
selection of appropriate RBC units is more complex. D-negative units
are more likely to be identified among European donors. Therefore,
providing D-negative RBCs to patients with partial D antigen status
may increase alloimmunization risk to other antigens (Fy a, Jk b, and
S) more common in Europeans compared with Africans. Approximately
80% of African individuals are E negative. Therefore, providing e-negative
RBCs for patients with partial e status may result in unwanted anti-E
alloimmunization. In the future, minimizing Rh alloimmunization will
require recruitment and retention of repeat African American donors
with molecular RBC characterization including RH. Studies are needed
to determine whether RH genetically compatible RBCs could prevent
Rh alloimmunization and improve clinical outcomes.
Prophylactic antigen matching beyond C, E, and K has been proposed
to further reduce alloimmunization in SCD [31,32], which would require
extensive recruitment of ethnically matched donors. The availability of
high-throughput RBC genotyping for both patient and donor popula-
tions and a national donor database could facilitate an extended RBC
matching strategy. To date, a few feasibility studies have investigated
whether molecular typing of patients and donor inventories could
provide extended matched RBCs to patients with SCD (matched at
ABO, RhD, C/c, E/e, K, Fy a/Fy b, Jk a/Jk b, S/s, +/−Dombrock, and +/−
Diego) [33,34]. A small fraction of patients (7%–8%) had no extended
matched components available due to a predominantly Caucasian
donor pool in 1 study [33] or infrequent or rare patient phenotypes
[34]. Further research is needed to determine whether maintenance of
a large pool of ethnically matched, molecularly typed donors is feasible
and could reduce alloimmunization.
Thalassemia
Alloimmunization is common in patients with thalassemia requiring
chronic RBC transfusions. Red blood cell genotyping has not been used
routinely in this patient population but should be considered for
extended RBC antigen profiling for reasons discussed above for chronic
transfusion recipients.
Autoimmune Hemolytic Anemia and Warm Autoantibodies
Knowledge of the patient's RBC phenotype can guide alloantibody
evaluation and donor RBC selection, but is usually not available for
patients with autoimmune hemolytic anemia. Advanced serological
phenotyping techniques such as enzyme treatment can be used to
remove autoantibodies from the RBC membrane but may degrade
some blood group antigens leading to false-negative or inconclusive
results [1]. Alternatively, molecular RBC antigen typing may be used to
improve transfusion safety by determining the patient's extended RBC
antigen profile, facilitating absorption studies and alloantibody evalua-
tions, guiding provision of prophylactic antigen-matched RBCs, and
circumventing pretransfusion adsorption studies [24,35].
Blood Donors
Large-scale donor genotyping facilitates identification of donors
with rare blood types or uncommon RBC phenotypes that are negative
for multiple antigens. Studies have demonstrated that donor RBC
genotyping to provide antigen-negative RBCs regionally fulfilled greater
than 90% of requests [2,33,34,36]. Further, large-scale RHD and RHCE
molecular analysis performed on African blood donors in France
(established by Fy[a-b-] phenotype) provided indirect evidence that
the transfusion needs of patients with SCD and anti-Rh antibodies
may potentially be met by screening very large populations of donors
for RH variant phenotypes [37]. Combined with real-time inventory
databases shared between blood centers and transfusion services,
large-scale donor genotyping has the potential to improve the efficiency
of supplying antigen-negative RBC units. See Table for potential patient
and blood donor RBC genotyping indications.
Summary/Research Priorities
The application of blood group genotyping into clinical practice will
necessitate cost-efficient technology, broader adoption by transfusion
service laboratories, and determination of its impact on patient out-
comes. As next-generation sequencing methods improve, accurate
ABO and Rh blood group prediction will likely become feasible. The
clinical relevance of RH variation in SCD and weak D status in pregnant
females for RhIg prophylaxis are 2 areas already identified that may
justify genotyping cost. However, future efforts are needed to identify
specific genetic variants that predispose to alloimmunization, to find
efficient approaches for patient-donor matching by DNA-predicted
 R.M. Fasano, S.T. Chou / Transfusion Medicine Reviews 30 (2016) 197–201 201

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