Fetal RHD screening for targeted routine antenatal anti-D prophylaxis has been implemented in many countries, including Finland, since the 2010s. Comprehensive knowledge of the RHD polymorphism in the population is essential for the performance and safety of the anti-D prophylaxis program. During the first 3 years of the national screening program in Finland, over 16 000 samples from RhD− women were screened for fetal RHD; among them, 79 samples (0.5%) containing a maternal variant allele were detected. Of the detected maternal variants, 35 cases remained inconclusive using the traditional genotyping methods and required further analysis by next-generation sequencing (NGS) of the whole RHD gene to uncover the variant allele. In addition to the 13 RHD variants that have been previously reported in different populations, 8 novel variants were also detected, indicating that there is more variation of RHD in the RhD− Finnish population than has been previously known. Three of the novel alleles were identified in multiple samples; thus, they are likely specific to the original Finnish population. National screening has thus provided new information about the diversity of RHD variants in the Finnish population. The results show that NGS is a powerful method for genotyping the highly polymorphic RHD gene compared with traditional methods that rely on the detection of specific nucleotides by polymerase chain reaction amplification.

Genetic variation in the MICA and MICB genes located within the major histocompatibility complex region has been reported to be associated with transplantation outcome and susceptibility to autoimmune diseases and infections. Only limited data of polymorphism in these genes in different populations are available. We here report allelic variation at 2‐field resolution and the haplotypes of the MICA and MICB genes in Finland (n = 1032 individuals), a north European population with historical bottleneck and founder effects. Altogether 24 MICA and 18 MICB alleles were found, forming 70 estimated MICA‐MICB haplotypes. As compared to other populations frequency differences were found, for example, MICA*010:01 was found to be at an allele frequency of 0.133 in Finland which is higher than in other European populations (0.021–0.077), but close to Asian populations (0.151–0.220). Three novel alleles with amino acid change are described. The results demonstrate a relatively high level of polymorphism and population differences in MICA and MICB allele distribution.

Background Nanopore sequencing is direct sequencing of a single-stranded DNA molecule using biological pores. A portable nanopore-based sequencing device from Oxford Nanopore Technologies (MinION) depends on driving a DNA molecule through nanopores embedded in a membrane using a voltage. Changes in current are then measured by a sensor, thousands of times per second and translated to nucleobases. Methods Genomic DNA (gDNA) samples (n = 13) were tested for Rh blood group D antigen (RHD) gene zygosity using droplet digital PCR. The RHD gene was amplified in 6 overlapping amplicons using long-range PCR. Amplicons were purified, and the sequencing library was prepared following the 1D Native barcoding gDNA protocol. Sequencing was carried out with 1D flow cells R9 version. Data analysis included basecalling, aligning to the RHD reference sequence, and calling variants. Variants detected were compared to the results acquired previously by the Ion Personal Genome Machine (Ion PGM). Results Up to 500× sequence coverage across the RHD gene allowed accurate variant calling. Exonic changes in the RHD gene allowed RHD allele determination for all samples sequenced except 1 RHD homozygous sample, where 2 heterozygous RHD variant alleles are suspected. There were 3 known variant RHD alleles (RHD*01W.02, RHD*11, and RHD*15) and 6 novel RHD variant alleles, as previously seen in Ion PGM sequencing data for these samples. Conclusions MinION was effective in blood group genotyping, provided enough sequencing data to achieve high coverage of the RHD gene, and enabled confident calling of variants and RHD allele determination.

Backround Health questionnaires and donation criteria result to accumulation of highly selected individuals in blood donor population. To understand better the usefulness of blood donor-based biobank in personalised disease-associated genetic studies and for possible personalised blood donation policies we evaluated the occurrence and distributions of common and rare disease-associated genetic variants in Finnish Blood Service Biobank. Methods We analysed among 31,880 blood donors the occurrence and geographical distribution of (i) 53 rare Finnish enriched disease-associated variants, (ii) mutations assumed to influence blood donation: four Bernard-Soulier syndrome and two hemochromatosis mutations, (iii) type I diabetes risk genotype HLA-DQ2/DQ8. In addition, we analysed the level of consanguinity in Blood Service Biobank. Results 80.3% of blood donors carried at least one (range 0–9 per donor) of the rare variants, many in homozygous form as well. Donors carrying multiple rare variants were enriched in the Eastern Finland. Haemochromatosis mutation HFE C282Y homozygosity was 43.8% higher than expected, whereas mutations leading to Bernard-Soulier thrombocytopenia were rare. The frequency of HLA-DQ2/DQ8 genotype was slightly lower than in the general population. First-degree consanguinity was higher in Blood Service Biobank than in the general population. Conclusion We demonstrate that despite donor selection the Blood Service Biobank is a valuable resource for personalised medical research and for genotype-selected samples from unaffected individuals. Geographical genetic substructure of Finland enables efficient recruitment of donors carrying rare variants. Furthermore, we show that blood donor biobank material can be utilized for personalized blood donation policies.