Developments beyond blood group serology in the genomics era

Hyland, Catherine A.; Roulis, Eileen; Schoeman, Elizna M.

doi:10.1111/bjh.15747

Cited by 13 publications

(10 citation statements)

References 106 publications

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“…With ongoing international interest and emerging ambitious genomics initiatives [9], genomics data size is predicted to surpass that of all other scientific fields by the year 2025 [10]. In transfusion medicine, next generation sequencing (NGS) has promising new applications given its sensitivity for microchimerism and copy number detection, and its potential to detect all known as well as novel blood group gene variations in a single assay [11–13]. We propose that blood antigen interpretation is a universal clinical benefit that could increase the cost‐efficiency of genomic sequencing performed in the clinical setting [14].…”

Section: Introductionmentioning

confidence: 99%

An open‐source python library for detection of known and novel Kell, Duffy and Kidd variants from exome sequencing

Montemayor

Simone

Long³

et al. 2021

Vox Sanguinis

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Background and objectives Next generation sequencing (NGS) has promising applications in transfusion medicine. Exome sequencing (ES) is increasingly used in the clinical setting, and blood group interpretation is an additional value that could be extracted from existing data sets. We provide the first release of an open‐source software tailored for this purpose and describe its validation with three blood group systems. Materials and methods The DTM‐Tools algorithm was designed and used to analyse 1018 ES NGS files from the ClinSeq® cohort. Predictions were correlated with serology for 5 antigens in a subset of 108 blood samples. Discrepancies were investigated with alternative phenotyping and genotyping methods, including a long‐read NGS platform. Results Of 116 genomic variants queried, those corresponding to 18 known KEL, FY and JK alleles were identified in this cohort. 596 additional exonic variants were identified KEL, ACKR1 and SLC14A1, including 58 predicted frameshifts. Software predictions were validated by serology in 108 participants; one case in the FY blood group and three cases in the JK blood group were discrepant. Investigation revealed that these discrepancies resulted from (1) clerical error, (2) serologic failure to detect weak antigenic expression and (3) a frameshift variant absent in blood group databases. Conclusion DTM‐Tools can be employed for rapid Kell, Duffy and Kidd blood group antigen prediction from existing ES data sets; for discrepancies detected in the validation data set, software predictions proved accurate. DTM‐Tools is open‐source and in continuous development.

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Section: Introductionmentioning

confidence: 99%

An open‐source python library for detection of known and novel Kell, Duffy and Kidd variants from exome sequencing

Montemayor

Simone

Long³

et al. 2021

Vox Sanguinis

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“…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].…”

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

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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.

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“…The Duffy null phenotype was not found amongst all other populations consistent with earlier reports. 11,49 We report for the first time the distribution of a rare parabombay H+ type (FUT2*01W.02.01), which was found only among the ASPREE (0.07%, n=2) and East Asian (19.05%, n=96) populations and was not represented in the European dataset. We also found a very low percentage of the extremely rare Kel 6,-7 antigen (0.15%) previously reported frequency in African populations is 19% and in Caucasians <1% 50 .…”

Section: Distribution Of Weak Partial and Null Antigensmentioning

confidence: 86%

Using Whole Genome Sequencing to Characterize Clinically Significant Blood Groups Among Healthy Older Australians

Jadhao

Davison

Roulis

et al. 2021

Preprint

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There have been no comprehensive studies of a full range of blood group polymorphisms within the Australian population. The problem is compounded by the absence of any databases carrying genomic information on chronically transfused patients and low frequency blood group antigens in Australia. Here, we use RBCeq, a web server-based blood group genotyping software, to identify unique blood group variants among Australians and compare the variation detected versus global data. Whole genome sequencing data was analysed from for 2796 healthy older Australians from the Medical Genome Reference Bank and compared with data from 1000G phase 3 (1KGP3) databases comprising 661 African, 347 American, 503 European, 504 East Asian, and 489 South Asian participants. There were 688 rare variants detected in this Australian sample population, including nine variants that had clinical associations. Notably, we identified 149 variants that were computationally predicted to be novel and deleterious. No clinically significant rare or novel variants were found associated with the genetically complex ABO blood group system. For the Rh blood group system one novel and 16 rare variants were found. Our detailed blood group profiling results provide a starting point for the creation of an Australian blood group variant database.

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Developments beyond blood group serology in the genomics era

Cited by 13 publications

References 106 publications

An open‐source python library for detection of known and novel Kell, Duffy and Kidd variants from exome sequencing

An open‐source python library for detection of known and novel Kell, Duffy and Kidd variants from exome sequencing

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

Using Whole Genome Sequencing to Characterize Clinically Significant Blood Groups Among Healthy Older Australians

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