Approaches to Determination of a Full Profile of Blood Group Genotypes: Single Nucleotide Variant Mapping and Massively Parallel Sequencing

摘要

The number of blood group systems, currently 35, has increased in the recent years as genetic variations defining red cell antigens continue to be discovered. At present, 44 genes and 1568 alleles have been defined as encoding antigens within the 35 blood group systems. This paper provides a brief overview of two genetic technologies: single nucleotide variant (SNV) mapping by DNA microarray and massively parallel sequencing, with respect to blood group genotyping. The most frequent genetic change associated with blood group antigens are SNVs. To predict blood group antigen phenotypes, SNV mapping which involves highly multiplexed genotyping, can be performed on commercial microarray platforms. Microarrays detect only known SNVs, therefore, to type rare or novel alleles not represented in the array, further Sanger sequencing of the region is often required to resolve genotype. An example discussed in this article is the identification of rare and novel RHD alleles in the Australian population. Massively parallel sequencing, also known as next generation sequencing, has a high-throughput capacity and maps all points of variation from a reference sequence, allowing for identification of novel SNVs. Examples of the application of this technology to resolve the genetic basis of orphan blood group antigens are presented here. Overall, the determination of a full profile of blood group SNVs, in addition to serological phenotyping, provides a basis for provision of compatible blood thus offering improved transfusion safety.