Skip to main content

Blood Bank

Genetics

Basic genetics tells us what we inherit (alleles) and the rules of expression (dominance/codominance). Molecular genetics explains how tiny differences in DNA create those different alleles and antigens. Inheritance patterns describe how these alleles are transmitted through generations, often influenced by whether the genes are linked together on chromosomes. Together, these principles form the foundation for understanding blood group diversity and its critical implications in transfusion medicine

Think of blood group genetics like building with LEGOs® following specific instructions:

The Instructions (Basic Genetics)

  • Our traits, like blood type, are determined by genes, specific sections of our DNA blueprint found at particular addresses called loci on our chromosomes
  • Genes come in different versions called alleles (e.g., A, B, O alleles for the ABO gene). We inherit one allele from each parent
  • Our specific inherited pair of alleles is our genotype (e.g., AO). What we actually detect on the red cells in the lab is the phenotype (e.g., Group A)
  • Alleles can interact: Codominant ones (like A and B) both show up if inherited together (AB phenotype). A dominant allele (like D in Rh) shows up even if paired with a recessive one (d), which only shows its trait if two copies are present (dd)

Decoding the Instructions (Molecular Genetics)

  • The difference between alleles lies in their specific DNA sequence (the order of A, T, C, G bases)
  • Variations like Single Nucleotide Polymorphisms (SNPs) – a change in just one DNA base – are very common. Other variations include insertions/deletions (indels)
  • These DNA changes can alter the protein the gene codes for. This protein might be the antigen (like Rh or Kell proteins) or it might be an enzyme (like the ABO glycosyltransferases) that builds a carbohydrate antigen
  • Example: A few specific SNPs differentiate the A and B alleles, changing the enzyme they produce, which in turn adds a different sugar to make the A or B antigen. A deletion causing a frameshift often leads to a non-functional enzyme, resulting in the O allele
  • Molecular techniques (like PCR-based methods) allow us to directly read the DNA sequence (genotyping) to predict the phenotype, which is invaluable for complex cases, recently transfused patients, or fetal testing

Passing Down the Instructions (Inheritance)

  • We inherit alleles according to Mendel’s Laws:
    • Segregation: Each parent passes only one of their two alleles for a gene to their offspring
    • Independent Assortment: Genes for different traits on different chromosomes are inherited independently (e.g., ABO type doesn’t influence Rh type)
  • Exception - Linkage: Genes located close together on the same chromosome (like RHD and RHCE, or GYPA and GYPB for MNS) are often inherited as a block, called a haplotype (e.g., DCe, Ns)
  • Punnett squares: help predict the probability of offspring inheriting specific genotypes and phenotypes based on parental genotypes
  • Understanding inheritance helps explain family patterns, predict risk for Hemolytic Disease of the Fetus and Newborn (HDFN), and understand why certain antibodies might be formed