A baby’s blood type is determined by the combination of genes inherited from both parents, one copy from the mother and one from the father, at two independent genetic locations: the ABO gene on chromosome 9 and the RHD gene on chromosome 1. Because each parent contributes one version of each gene, a baby’s blood type is constrained by but not identical to the parents’ types. The interplay between dominant and recessive versions of these genes, along with rare mutations and variants, means the system holds more surprises than most people expect.
How the ABO System Works
The ABO blood group comes down to sugar molecules on the surface of red blood cells. Every person carries two copies of the ABO gene, and each copy can be one of three main versions: A, B, or O. The A version produces an enzyme that sticks a specific sugar (N-acetylgalactosamine) onto a base molecule already sitting on the red cell surface. The B version produces a very similar enzyme that attaches a different sugar (galactose) instead. The O version produces a nonfunctional enzyme that adds nothing at all.
Because you have two copies, the combination you carry determines your blood type. If you inherit an A from one parent and an A or O from the other, your red cells display the A sugar and your blood type is A. The same logic applies to B. If you get an A from one parent and a B from the other, both enzymes work, both sugars appear, and your type is AB. If both copies are O, neither sugar gets added, and your type is O. The key point is that A and B are co-dominant with each other (both show up when present together) while O is recessive (it only shows its effect when no A or B version is around to override it).
This means a parent with blood type A could be carrying either two A copies or one A and one hidden O. The same goes for type B. A parent with type AB is carrying one A and one B, period. And a parent with type O always carries two O copies. These hidden possibilities are what make blood type inheritance less predictable than it first seems.
What Blood Types Can Parents Pass On
The possible blood types of a child depend entirely on the gene copies the parents actually carry, not just the blood type shown on a lab report. Two parents who are both type A, for example, could each be carrying a hidden O. If both happen to pass that O copy to their child, the baby will be type O, which surprises many families.
Some combinations are straightforward. Two type O parents can only have type O children. A type AB parent will always pass either an A or a B, so they can never have a type O child (barring rare exceptions discussed below). If one parent is type A (carrying A and O) and the other is type B (carrying B and O), their children could end up as A, B, AB, or O depending on which copy each parent passes along.
A child always inherits one allele from each biological parent. If a child carries an allele that neither parent could have contributed, that raises questions about biological parentage. At least one parent must share at least one allele in common with the child for the relationship to hold up genetically.1Information Technology International Journal. The Possibility Prediction of Inheriting Blood Types in Parents Based on The Child’s Allele Combination This principle is why blood typing was historically used in paternity disputes, though modern DNA tests are far more powerful.
The Rh Factor
The second part of a blood type label is the “positive” or “negative,” which refers to the Rh D protein on the red cell surface. This is controlled by a separate gene called RHD on chromosome 1. People who are Rh-positive have at least one working copy of RHD that produces the D protein. People who are Rh-negative typically lack the RHD gene entirely on both chromosomes.
Researchers confirmed this in the early 1990s by showing that the mRNA and gene sequences for the D protein were present in Rh-positive individuals but completely absent in Rh-negative individuals.2Blood. Molecular cloning of RhD cDNA derived from a gene present in RhD-positive, but not RhD-negative individuals Because having at least one working copy is enough to produce the protein, Rh-positive is dominant over Rh-negative. A baby can only be Rh-negative if both parents contribute a chromosome that lacks a functional RHD gene. Two Rh-positive parents who each carry one nonfunctional copy have a one-in-four chance of having an Rh-negative child.
The Rh factor matters enormously during pregnancy. If an Rh-negative mother carries an Rh-positive baby, her immune system can develop antibodies against the baby’s D protein. This is called Rh sensitization, and it rarely causes problems in a first pregnancy but can lead to serious anemia in subsequent Rh-positive pregnancies. A preventive injection of Rh immune globulin (commonly known by the brand name RhoGAM) is given to Rh-negative mothers during pregnancy and after delivery to stop the immune response from forming.
Weak D and the Gray Area of Rh Typing
The positive-or-negative distinction sounds simple, but roughly 0.2 to 1 percent of routine Rh typings return a result in between, called a serological weak D phenotype.3PubMed Central. Serological weak D phenotypes: a review and guidance for interpreting the RhD blood type using the RhD genotype These individuals produce a D protein, but either in reduced quantities or in a slightly altered form that doesn’t react strongly in standard lab tests. In many cases the person is functionally Rh-positive and faces no clinical risk from Rh-positive blood.
For pregnant women, the distinction matters. If a woman with a weak D type is misidentified as Rh-negative, she may receive unnecessary Rh immune globulin injections. Conversely, if she has a partial D variant that genuinely puts her at risk of forming anti-D antibodies, skipping the injection could be dangerous. Genetic testing can identify the specific RHD variant and guide the clinical decision. Research in Chinese blood donors, for instance, has identified specific gene variations that help distinguish weak D and DEL (an extremely weak D expression) from truly Rh-negative status.4PubMed Central. Effects of RHD gene polymorphisms on distinguishing weak D or DEL from RhD- in blood donation in a Chinese population The most common weak D types in people of European descent (types 1, 2, and 3) can safely be managed as Rh-positive, which conserves limited Rh-negative blood supplies and spares mothers unnecessary treatment.
When the Standard Rules Break Down
Every genetics textbook presents ABO inheritance as a tidy three-allele system, but real biology occasionally throws curve balls. The most notable is cis-AB, a rare variant in which a single copy of the ABO gene produces an enzyme capable of attaching both the A and B sugars. Instead of getting A from one parent and B from the other, a person with cis-AB inherited both activities from the same parent on one chromosome.5PubMed Central. Cis-AB, the Blood Group of Many Faces, Is a Conundrum to the Novice Eye
This means a parent who is type O and a parent who carries cis-AB can have a child who appears to be type AB. Under normal rules, that’s impossible, since a type O parent has nothing but O alleles to give. In one documented case, a child who serologically typed as AB was confirmed through genetic markers to be the biological child of a type O father. Sequencing showed the child carried one O allele from the father and a cis-AB allele (derived from the A transferase gene with a single point mutation) from the mother.6Annals of Clinical & Laboratory Science. A Novel cis-AB Allele Derived from the A Transferase Gene by Nucleotide Substitution C796A Another cis-AB allele was traced to a mutation in a B allele, where a single nucleotide change gave the B enzyme partial A activity as well.7PubMed. A novel cis AB allele derived from a B allele through a single point mutation These variants are rare but have been found across multiple populations, and they are important to recognize in paternity testing and transfusion medicine because they can look like impossible parentage results.
An even rarer exception is chimerism, where a single person carries two genetically distinct cell lines. This can happen naturally when fraternal twin embryos fuse early in development (tetragametic chimerism) or exchange blood through shared placental connections. A chimeric individual can carry three or even four different ABO alleles in different tissues. One reported case involved a person whose blood cells carried both A/O and B/O genotypes simultaneously, making standard blood typing confusing.8PubMed. Congenital tetragametic blood chimerism explains a case of questionable paternity Another chimeric individual appeared to be type AB with an unusual mixed-field agglutination pattern, but molecular testing revealed A, B, and O alleles were all present.9PubMed. Tetragametic chimerism detected in a healthy woman with mixed-field agglutination reactions in ABO blood grouping A third case initially looked like an unusual B subtype but turned out to be a dispermic chimera with a third ABO allele, confirmed through detailed genetic analysis.10PubMed Central. A dispermic chimera with mixed field blood group B and mosaic 46,XY/47,XYY karyotype
These cases are genuinely unusual and most families will never encounter them. But they explain the occasional news story about a paternity test or blood type result that seems to defy basic genetics. When standard inheritance rules produce an impossible answer, the explanation is almost always one of these rare variants rather than a lab error.
Blood Groups Beyond ABO and Rh
ABO and Rh get all the attention, but the International Society of Blood Transfusion recognizes over 40 blood group systems. Most of them rarely cause problems in everyday transfusions, but a few become relevant during pregnancy. After the D antigen, the most clinically potent immunogenic antigen is K (also called KEL1 or Kell). Kell alloimmunization affects roughly 0.1 to 0.3 percent of pregnancies and accounts for about 10 percent of cases of antibody-mediated severe fetal anemia.11PubMed Central. Approach to Pregnancy Affected by Kell Alloimmunization
Kell antibodies work differently from Rh antibodies. Rh disease primarily destroys circulating fetal red blood cells, but Kell antibodies also suppress the fetal bone marrow’s ability to produce new red cells in the first place, which can make the anemia more severe and harder to predict with standard monitoring. Unlike Rh disease, there is no preventive immune globulin injection for Kell sensitization. Exposure usually happens through a blood transfusion with Kell-positive blood, though it can also occur during pregnancy. Because no prophylaxis exists, Kell-sensitized pregnancies require close surveillance, and in severe cases, intrauterine transfusions can be lifesaving.12PubMed. Successful treatment of extremely severe fetal anemia due to Kell alloimmunization An increasing incidence of anti-Kell antibodies has been noted in the United States, likely due to transfusion exposure, and these pregnancies are managed more conservatively than Rh-sensitized ones.13PubMed. Fetal anemia due to non-Rhesus-D red-cell alloimmunization
A baby inherits Kell status the same way it inherits other blood group antigens: one gene copy from each parent. Most people are Kell-negative (they lack the K antigen), and a Kell-positive father with a Kell-negative mother creates the mismatch that can trigger sensitization. The inheritance principle is the same as for Rh, but the clinical management differs because of the bone marrow suppression mechanism.
Testing a Baby’s Blood Type Before Birth
For most pregnancies, there is no medical need to know the baby’s blood type before delivery. But when a mother has been sensitized to a blood group antigen, identifying the fetal blood type early can determine whether the pregnancy is even at risk and guide how aggressively to monitor.
The breakthrough that changed prenatal blood typing was the discovery that fetal DNA circulates freely in the mother’s blood during pregnancy. First described in the early 1990s, the technique of analyzing this cell-free fetal DNA has matured into a reliable clinical tool. For Rh typing specifically, the sensitivity and specificity of these noninvasive assays now approach 99 percent.14American Journal of Obstetrics & Gynecology. Noninvasive prenatal testing for fetal RhD status: the time has come Scandinavian countries have integrated cell-free DNA testing into routine prenatal care for all Rh-negative women, using the result to decide whether Rh immune globulin is needed at all, rather than giving it universally and sometimes unnecessarily.
Next-generation sequencing has broadened the range of fetal blood group antigens that can be detected from a maternal blood draw. Because many blood group differences come down to a single nucleotide change in the DNA, sequencing can identify the fetal type for Kell, Duffy, Kidd, and other clinically relevant systems alongside Rh, all from the same sample and with no risk to the fetus.15PubMed Central. Noninvasive Antenatal Determination of Fetal Blood Group Using Next-Generation Sequencing In the United States, commercial noninvasive prenatal testing panels now include fetal RHD genotyping, and the technology is likely to expand further.
Why a Newborn’s Blood Type Can Look Different From the Final Result
If your baby’s blood is typed at birth, the result is usually accurate for Rh status but sometimes ambiguous for ABO. This is because ABO antigens on fetal red blood cells are weaker than on adult cells. A study that tested fetal blood obtained during the second and third trimesters found that A, B, and H antigens all showed significantly reduced expression compared to adult red cells.16Pediatric Research. Blood Group Antigens on Fetal Red Cells Obtained by Umbilical Vein Puncture under Ultrasound Guidance The A and B antigens continue to strengthen after birth and reach adult levels within the first few years of life.
This weak expression occasionally leads to a newborn being typed as O when they are actually A or B, simply because the lab reagents don’t react strongly enough with the baby’s underdeveloped surface antigens. If a newborn’s type seems inconsistent with the parents’, repeating the test at a few months of age usually resolves the discrepancy. Rh typing is more straightforward in newborns because the D antigen is generally well-expressed at birth.
Blood Type Frequency Around the World
The distribution of ABO blood types varies dramatically by population and geography. Globally, type O is the most common, but its frequency ranges from about 40 percent in many European countries to well over 90 percent in some Indigenous populations of Central and South America. Type B is relatively common in Central and South Asia but rare in Indigenous peoples of the Americas and Australia. These patterns are not random. The global distribution of ABO blood groups has been shaped by environmental factors including disease pressure, climate, and population migration history.17PubMed Central. A brief history of human blood groups
Malaria appears to be one of the strongest selective pressures. Research has found that the geographic distribution of type O is consistent with a selection advantage for O individuals in malaria-endemic regions, because the parasite Plasmodium falciparum forms smaller and less dangerous clumps on type O red blood cells compared to types A, B, or AB.18PubMed. The ABO blood group system and Plasmodium falciparum malaria This means the blood type your baby inherits is, in a deep evolutionary sense, partly a legacy of which diseases your ancestors faced.
A Surprisingly Ancient Genetic System
The A and B alleles of the ABO gene are not a recent human invention. Genetic analysis of primates has revealed that the split between A and B alleles predates the divergence of many primate species. In macaques, baboons, and colobus monkeys, the genetic diversity between A and B alleles is enormous, exceeding even the divergence between these separate species. Shared genetic signatures across these groups indicate that the A/B polymorphism originated at least 18 million years ago and has been maintained ever since across multiple primate lineages.19PubMed Central. The ABO blood group is a trans-species polymorphism in primates
This is what evolutionary biologists call a trans-species polymorphism: a genetic variation so old that it predates the species carrying it. Maintaining both A and B versions for tens of millions of years suggests that having variation in the population is actively beneficial, likely because different blood types confer different levels of resistance to different pathogens. The human O allele arose later through mutations that broke the enzyme, and it appears to have been favored in regions with heavy malaria burden.
Toward Universal Donor Blood Through Enzyme Engineering
Understanding that ABO blood types come down to different sugars on the red cell surface has opened an intriguing line of research: what if you could simply remove the A or B sugars from donated blood, converting it all to type O? Type O red cells lack both sugars and can be given to any ABO type in an emergency, so enzymatic conversion would effectively create a universal supply from any donor.
Researchers have been working on this idea for decades, and recent advances have made it far more practical. A team screening microbial enzymes found a highly efficient two-enzyme system in the gut microbiome of a type AB blood donor. These enzymes, a deacetylase paired with a galactosaminidase, strip the A antigen from red cells using roughly 15- to 30-fold less enzyme than the previous best candidate. They work in whole blood at room temperature or refrigerator temperature, and the enzymes can be removed by the same centrifugation steps already used in standard blood processing. As little as one milligram of enzyme per unit of blood may be sufficient for full conversion.20PubMed Central. Toward universal donor blood: Enzymatic conversion of A and B to O type
This technology is still being refined and has not entered routine clinical use, but it represents a potential future in which the ABO matching constraints that currently complicate blood banking could be largely eliminated. The sugars that determine your baby’s blood type may, one day, be removable on demand.
When Cancer Alters Blood Type Expression
Blood type is normally fixed for life, determined at conception and unchanged through adulthood. But there is one context in which ABO expression can shift: cancer. Certain tumors can silence the ABO gene through a chemical modification called promoter methylation, which essentially switches the gene off without changing the DNA sequence itself. In a study of oral squamous cell carcinomas, about a third of tumors showed this kind of methylation, and the silencing was linked to loss of A or B antigen expression on the tumor cells.21PubMed. Genetic and epigenetic alterations of the blood group ABO gene in oral squamous cell carcinoma
This doesn’t change the person’s blood type on a lab test drawn from normal blood. But it means the tumor cells may display a different surface profile than the rest of the body, which has implications for how the immune system recognizes the cancer and for how researchers think about tumor biology. It is a reminder that while your ABO genotype is set at conception, the expression of those genes in specific tissues can be more dynamic than the simple inheritance story suggests.