MN typing discrepancies based on GYPA-B-A hybrid

Area of Science:

• Genetics
• Molecular Biology
• Blood Group Serology

Background:

• Gene conversion between GYPA and GYPB/GYPE can create hybrid genes due to sequence homology.
• Discrepancies between blood group genotyping and hemagglutination prompted molecular investigation in 22 donors.

Purpose of the Study:

• To characterize the molecular basis of discrepancies observed in blood group genotyping and hemagglutination.
• To identify and analyze novel hybrid genes formed through recombination events.

Main Methods:

• Sequence analysis of GYPA and GYPB exons using genomic DNA (gDNA) and complementary DNA (cDNA).
• Haplotype separation to determine the linkage of nucleotide alterations.

Main Results:

• A GYPA-B-A hybrid gene was identified, characterized by a GYPB sequence integrated into GYPA.
• This hybrid gene resulted in an amino acid substitution but did not alter M and N antigen expression.
• A heterozygous deletion of GYPB exon 2 was observed in all subjects.

Conclusions:

• The findings document a GYPA-B-A hybrid gene, likely resulting from a single unequal homologous recombination event.
• Segmental transfer of GYPB sequences appears to be the mechanism leading to the observed allelic dropout.