Deciphering the Genetic Mystery: Type O Blood in Offspring of Type A Parents Explained


The inheritance of blood types has long captivated geneticists and researchers, offering insights into the complexities of genetic inheritance. The ABO blood group system, a classic paradigm of human inheritance, showcases the interplay of genes and alleles in determining the ABO blood types—A, B, AB, and O (National Center for Biotechnology Information [NCBI], 2018). While the inheritance patterns of blood types are relatively well understood, intriguing scenarios emerge when two biological parents with type A blood produce offspring expressing type O blood. This essay explores the genetic mechanisms underlying this phenomenon, delving into the vocabulary of dysmorphology and referencing the American Journal of Medical Genetics (AJMG) Special Issue (Wiley Online Library, 2019) to elucidate this intriguing facet of inheritance.

Understanding the ABO Blood Group System

The foundation of comprehending blood type inheritance lies in understanding the ABO blood group system. This system hinges on the presence of two antigens—A and B—on the surface of red blood cells, which interact with corresponding antibodies. The combination of antigens and antibodies determines an individual’s blood type, offering a glimpse into the complex interplay between genetic alleles and protein expression.

Genetic Basis of Blood Type Inheritance

The genetic basis of blood type inheritance is rooted in the ABO gene, situated on chromosome 9. The gene harbors three primary alleles: A, B, and O. When individuals inherit alleles from both parents, a multitude of genotypes can emerge, leading to distinct blood type phenotypes.

Type A Blood: The presence of genotype AA or AO gives rise to type A blood. The A allele guides the production of antigen A on red blood cells, which reacts with anti-A antibodies.

Type B Blood: Genotype BB or BO generates type B blood. The B allele prompts the synthesis of antigen B on red blood cells, leading to compatibility with anti-B antibodies.

Type AB Blood: Genotype AB yields type AB blood, where both A and B alleles are present, causing the expression of both antigens on the cell surface. Consequently, individuals with type AB blood can receive blood from any ABO group without an immune response.

Type O Blood: Genotype OO results in type O blood. The O allele fails to produce either antigen, resulting in universal donors as they lack A or B antigens.

Epistasis and Type O Blood in Offspring of Type A Parents

The puzzle of type O blood arising in offspring of two type A parents can be resolved through the lens of epistasis—an intricate genetic interaction where the effects of one gene are influenced by another (Sulem et al., 2015). In this context, the ABO gene interacts with another gene, the H gene (FUT1), encoding the enzyme fucosyltransferase. This enzyme catalyzes the addition of fucose molecules to the precursor structure of ABO antigens, pivotal for antigen formation.

For individuals with functional H alleles, fucosyltransferase attaches fucose molecules to precursor antigens, culminating in the A or B antigens. However, individuals with non-functional H alleles (hh) are unable to attach fucose molecules, masking the presence of A or B alleles. As a result, even if individuals inherit A or B alleles from their parents, the corresponding antigens are unable to manifest fully due to the absence of fucose molecules. This intricate interaction between ABO and H genes leads to the phenotype of type O blood, even when parentage suggests type A blood inheritance.

Supporting Insights from Dysmorphology Vocabulary and AJMG Special Issue

Dysmorphology, the study of structural anomalies and genetic syndromes, offers insights into the genetic intricacies of blood type inheritance. The AJMG Special Issue extends these insights by spotlighting the role of epistasis in blood type determination (Wiley Online Library, 2019). The interplay between ABO and H genes, accentuated by specific genetic variations, showcases the nuances of inheritance.

The research presented in the AJMG Special Issue underscores the intricate relationships underlying blood type inheritance. By highlighting epistasis as a mechanism, the issue reinforces the significance of genetic interactions in shaping seemingly simple traits. Dysmorphology’s vocabulary enriches the conversation, providing a context to understand the genetic intricacies driving blood type inheritance anomalies.


Blood type inheritance, a classic genetic phenomenon, showcases the complexity underlying seemingly straightforward traits. The ABO blood group system’s intricacies are underpinned by the interplay between alleles, genes, and epistasis. The revelation of type O blood in offspring of type A parents finds its explanation in the subtle interactions between the ABO and H genes, revealing the depth of genetic relationships that influence our biological traits. The amalgamation of dysmorphology insights and AJMG research underscores the importance of dissecting genetic interactions to unravel enigmatic inheritance patterns. This phenomenon not only adds depth to our understanding of genetics but also emphasizes the intricate tapestry of nature’s genetic orchestration.


National Center for Biotechnology Information. (2018). Blood Group Systems.

Sulem, P., Helgason, H., Oddson, A., et al. (2015). Identification of a large set of rare complete human knockouts. Nature Genetics, 47(5), 448-452.

Wiley Online Library. (2019). American Journal of Medical Genetics (Special Issue).