Next‐generation sequencing: academic overkill or high‐resolution routine blood group genotyping?

<jats:p>Blood group genotyping (<jats:styled-content style="fixed-case">BGG</jats:styled-content>) has been in routine clinical practice ever since the molecular determination of blood groups was achieved, during the early to mid 1990s. These early methods were dependent on allele‐specific <jats:styled-content style="fixed-case">PCR</jats:styled-content> to detect simple single nucleotide polymorphisms (<jats:styled-content style="fixed-case">SNP</jats:styled-content>s) responsible for blood group expression. As our knowledge regarding the molecular background of blood groups advanced, so did the numbers of <jats:styled-content style="fixed-case">SNP</jats:styled-content>s requiring detection which necessitated the switch from allele‐specific <jats:styled-content style="fixed-case">PCR</jats:styled-content> to array‐based technology, notably slide and bead‐based approaches. All these methods thus described are totally dependent on the predefined genetic basis of each <jats:styled-content style="fixed-case">SNP</jats:styled-content>. Hybrid blood group genes (as found in <jats:styled-content style="fixed-case">RH</jats:styled-content>,<jats:styled-content style="fixed-case"> ABO</jats:styled-content> and <jats:styled-content style="fixed-case">MNS</jats:styled-content> systems) are difficult to define by all of these aforementioned techniques. With the arrival of cheap next‐generation sequencing (<jats:styled-content style="fixed-case">NGS</jats:styled-content>) approaches in the past 5 years, we have conducted long‐range <jats:styled-content style="fixed-case">PCR</jats:styled-content> (<jats:styled-content style="fixed-case">LR</jats:styled-content>‐<jats:styled-content style="fixed-case">PCR</jats:styled-content>) coupled with <jats:styled-content style="fixed-case">NGS</jats:styled-content> determination of the major blood group genes. By analysis of these data using an Ion Torrent Personal Genome Machine<jats:sup>™</jats:sup> (<jats:styled-content style="fixed-case">PGM</jats:styled-content><jats:sup>™</jats:sup>), it is readily apparent that <jats:styled-content style="fixed-case">NGS</jats:styled-content> can highly effectively be applied with high resolution to blood grouping at costs no more than current array‐based platforms. However, the complexity of the data obtained need careful filtering for effective clinical utilization, but provides useful insight on the evolution of blood groups and their environmental impacts which will be of undoubted value as an academic exercise, but of minimal cost (if any) to the original testing.</jats:p>