In the past few decades, blood group genotyping has greatly expanded our knowledge of the more prevalent alleles, paving the way for commercial genotyping assays. These assays have improved efficiency in providing genomic results, but understanding assay limitations can help direct additional investigations for complex cases.Variant alleles may affect protein expression and can be associated with alloimmunization risk after exposure through transfusion, pregnancy, or transplant. While genomic testing has increased understanding of altered antigens, alloimmunization risk remains unknown for many antigens encoded by variant alleles. Bioinformatic tools, including 3D protein modeling, can help assess the impact of amino acid changes encoded by variant alleles and provide insight into alloimmunization risk. When a variant allele is identified, blood bankers and clinicians must understand its clinical impact. In this program, we will review variant alleles, how we detect them, and the difficulty of predicting the risk of alloimmunization. We’ll propose using bioinformatics to gain insight into antigen expression in these cases.
Discuss common genetic mechanisms that lead to variant (or altered) alleles.
Describe genotyping methods used to detect and identify variant alleles, including limitations.
Explain the challenges of predicting alloimmunization risk and clinical significance of antibodies associated with variant antigens.
Discuss the use of in silico tools and 3D protein modeling to evaluate the effect of amino acid changes and provide insight into alloimmunization risk.
Manager, Education & Training, IRL/Genomic Laboratories,
New York Blood Center Enterprises
Etablissement francais du sang, Hopital Henri Mondor, Univ. Paris Est Creteil, INSERM U955, IMRB, Creteil, France
Technical Director, Genomics,
New York Blood Center