ABCG2 null alleles define the Jr(a-) blood group phenotype

Area of Science:

• Genetics
• Immunology
• Transfusion Medicine

Background:

• The Jr(a) blood group antigen is a high-frequency antigen in humans, important in transfusion medicine.
• Its genetic basis remained unknown for over 40 years, posing challenges in blood compatibility assessments.

Purpose of the Study:

• To identify the specific gene responsible for encoding the Jr(a) blood group antigen.
• To elucidate the genetic underpinnings of the Jr(a) null phenotype.

Main Methods:

• Single Nucleotide Polymorphism (SNP) analysis was performed on genomic DNA from six individuals lacking the Jr(a) antigen (Jr(a-)).
• A homozygous region on chromosome 4q22.1 was identified in all Jr(a-) individuals.
• DNA sequencing was used to analyze the gene within this region.

Main Results:

• A shared homozygous region of 397,000 base pairs was consistently found at chromosome 4q22.1 in all tested Jr(a-) individuals.
• This region contained the ATP-binding cassette sub-family G member 2 (ABCG2) gene.
• Sequence analysis confirmed that variations within the ABCG2 gene, specifically null alleles, are directly associated with the Jr(a-) phenotype.

Conclusions:

• The ATP-binding cassette sub-family G member 2 (ABCG2) gene encodes the Jr(a) blood group antigen.
• Jr(a) null individuals possess ABCG2 null alleles, providing a genetic explanation for this blood group.
• This discovery has significant implications for transfusion compatibility and understanding red blood cell antigen genetics.