Prediction of fetal blood group and platelet antigens from maternal plasma using next‐generation sequencing

Orzińska, Agnieszka; Guz, Katarzyna; Mikula, Michał; Kluska, Anna; Bałabas, Aneta; Ostrowski, Jerzy; Uhrynowska, Małgorzata; Kopeć, Izabella; Dębska, Marzena; Luterek, Katarzyna; Brojer, Ewa

doi:10.1111/trf.15116

Cited by 33 publications

(26 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Knowledge of the genetic variability in the ABO locus continues to accumulate as investigations are carried out [20,22,25]. Our discovery of a new variant among only 26 samples exemplifies this variability.…”

Section: Discussionmentioning

confidence: 98%

“…Blood group genotyping is used in clinical practice [13][14][15][16]. However, ABO genotyping is complicated, and despite successful development of assays for fetal RHD genotyping [17][18][19], or more recently for KEL and other non-RhD antigen targets [20][21][22], less work has been done attempting a noninvasive fetal ABO prediction [23]. Due to the huge genetic variation in the ABO locus [24,25], it is difficult to develop a simple assay that will reach 100% accuracy in different ethnic populations.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Next Generation Sequencing-Based Fetal ABO Blood Group Prediction by Analysis of Cell-Free DNA from Maternal Plasma

Rieneck

Hother

Clausen

et al. 2020

Transfus Med Hemother

View full text Add to dashboard Cite

Introduction: ABO blood group incompatibility between a pregnant woman and her fetus as a cause of morbidity or mortality of the fetus or newborn remains an important, albeit rare, risk. When a pregnant woman has a high level of anti-A or anti-B IgG antibodies, the child may be at risk for hemolytic disease of the fetus and newborn (HDFN). Performing a direct prenatal determination of the fetal ABO blood group can provide valuable clinical information. Objective: Here, we report a next generation sequencing (NGS)based assay for predicting the prenatal ABO blood group. Materials and Methods: A total of 26 plasma samples from 26 pregnant women were tested from gestational weeks 12 to 35. Of these samples, 20 were clinical samples and 6 were test samples. Extracted cell-free DNA was PCR-amplified using 2 primer sets followed by NGS. NGS data were analyzed by 2 different methods, FASTQ analysis and a grep search, to ensure robust results. The fetal ABO prediction was compared with the known serological infant ABO type, which was available for 19 samples. Results: There was concordance for 19 of 19 predictable samples where the phenotype information was available and when the analysis was done by the 2 methods. For immunized pregnant women (n = 20), the risk of HDFN was predicted for 12 fetuses, and no risk was predicted for 7 fetuses; one result of the clinical samples was indeterminable. Cloning and sequencing revealed a novel variant harboring the same single nucleotide variations as ABO*O.01.24 with an additional c.220C>T substitution. An additional indeterminable result was found among the 6 test samples and was caused by maternal heterozygosity. The 2 indeterminable samples demonstrated limitations to the assay due to hybrid ABO genes or maternal heterozygosity. Conclusions: We pioneered an NGS-based fetal ABO prediction assay based on a cell-free DNA analysis from maternal plasma and demonstrated its application in a small number of samples. Based on the calculations of variant frequencies and ABO*O.01/ABO*O.02 heterozygote frequency, we estimate that we can assign a reliable fetal ABO type in approximately 95% of the forthcoming clinical samples of type O pregnant women. Despite the vast genetic variations underlying the ABO blood groups, many variants are rare, and prenatal ABO prediction is possible and adds valuable early information for the prevention of ABO HDFN.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Next Generation Sequencing-Based Fetal ABO Blood Group Prediction by Analysis of Cell-Free DNA from Maternal Plasma

Rieneck

Hother

Clausen

et al. 2020

Transfus Med Hemother

View full text Add to dashboard Cite

show abstract

“…RBC genotyping has also increased the availability of RBC units for routine extended antigen matching in chronically transfused patients and has enabled selection of antigen‐matched units when compatibility cannot be demonstrated due to warm autoantibodies or drug interference in pretransfusion testing. Although single‐nucleotide polymorphism (SNP)‐based assays currently dominate the RBC and PLT genotyping market, next generation sequencing (NGS) approaches including targeted NGS, whole exome sequencing (WES), and whole genome sequencing (WGS) are being actively pursued by several groups …”

mentioning

confidence: 99%

Automated typing of red blood cell and platelet antigens from whole exome sequences

et al. 2019

View full text Add to dashboard Cite

for the MilSeq Project BACKGROUND: Genotyping has expanded the number red blood cell (RBC) and platelet (PLT) antigens that can readily be typed, but often represents an additional testing cost. The analysis of existing genomic data offers a cost-effective approach. We recently developed automated software (bloodTyper) for determination of RBC and PLT antigens from whole genome sequencing. Here we extend the algorithm to whole exome sequencing (WES). STUDY DESIGN AND METHODS: Whole exomesequencing was performed on samples from 75 individuals. WES-based bloodTyper RBC and PLT typing was compared to conventional polymerase chain reaction (PCR) RHD zygosity testing and serologic and single-nucleotide polymorphism (SNP) typing for 38 RBC antigens in 12 systems (17 serologic and 35 SNPs) and 22 PLT antigens (22 SNPs). Samples from the first 20 individuals were used to modify bloodTyper to interpret WES followed by blinded typing of 55 samples. RESULTS:Over the first 20 samples, discordances were noted for C, M, and N antigens, which were due to WES-specific biases. After modification, bloodTyper was 100% accurate on blinded evaluation of the last 55 samples and outperformed both serologic (99.67% accurate) and SNP typing (99.97% accurate) reflected by two Fy b and one N serologic typing errors and one undetected SNP encoding a Jk null phenotype. RHD zygosity testing by bloodTyper was 100% concordant with a combination of hybrid Rhesus box PCR and PCRrestriction fragment length polymorphism for all samples. CONCLUSION:The automated bloodTyper software was modified for WES biases to allow for accurate RBC and PLT antigen typing. Such analysis could become a routing part of future WES efforts.

show abstract

“…The fetal and maternal blood group and platelet antigen genotypes are determined with a targeted panel for sequencing and in parallel the antigen profile is provided for potential transfusions in the fetus and the mother. 83 The issue also concerns an important group of special donors relied upon for production of RBC panel reagents used for antibody screening and identification in all immunohematological laboratories worldwide. NGS typing of all blood group genes in these "products" will upgrade the interpretation of serological results and antigen matching.…”

Section: Applications Of Ngs In Transfusion Medicinementioning

confidence: 99%

<p>Potential of next-generation sequencing to match blood group antigens for transfusion</p>

Orzińska¹,

Guz²,

Brojer³

2019

IJCTM

Self Cite

View full text Add to dashboard Cite

A review of the advances in applying next-generation sequencing (NGS) to transfusion medicine for the purpose of genotyping alleles encoding clinically important red blood cell and platelet antigens. NGS data from published studies confirm the possibility of antigen prediction based on sequencing of the whole genome, exome or targeted regions. What remains a challenge, to provide highly accurate NGS genotyping, is the further improvement of bioinformatic solutions for automated interpretation based on publicly accessible and improved reference databases appropriate for NGS methods as well as validation of a method based on the examination of a large number of individuals. There is no doubt, however, as to the future of NGS as a supplementary test used to provide highly compatible blood as well as to reduce the risk of patient's alloimmunization. This is part of personalized medicine.

show abstract

Prediction of fetal blood group and platelet antigens from maternal plasma using next‐generation sequencing

Cited by 33 publications

References 14 publications

Next Generation Sequencing-Based Fetal ABO Blood Group Prediction by Analysis of Cell-Free DNA from Maternal Plasma

Next Generation Sequencing-Based Fetal ABO Blood Group Prediction by Analysis of Cell-Free DNA from Maternal Plasma

Automated typing of red blood cell and platelet antigens from whole exome sequences

<p>Potential of next-generation sequencing to match blood group antigens for transfusion</p>

Contact Info

Product

Resources

About