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Genetics of blood type: inheritance and compatibility

Medicover Genetics Editorial Team |
September 14th 2022

About 118.54 million blood donations are collected worldwide [1, WHO]. Knowing your blood type is important for medical reasons, e.g. if you require a blood transfusion or if you want to donate blood [4]. Blood typing is a fast and easy way to ensure that you receive the right blood type during surgery or after an injury. Incompatible blood can trigger a dangerous immune response. Blood typing is also important for pregnant women to prevent Rhesus incompatibility between mom and baby.

ABO blood types

The blood type is determined by the antigen on the surface of the red blood cells [2]. There are four main blood groups (A, B, AB, or O) and a Rhesus (Rh) factor (positive or negative). The blood type is passed down from our parents. The A and B alleles are co-dominant and the O allele is recessive [2].

Molecular basis

The ABO gene is located on chromosome 9 and has three alleles, A, B and O [3]. The A allele encodes a glycosyltransferase that adds N-acetylgalactosamine to the glycoprotein H antigen that is expressed on all normal red cells. The B allele encodes a different glycosyltransferase that adds d-galactose. The O allele is a deletion that results in loss of enzyme translation (inactive glycosyltransferase); therefore, resulting in an unmodified H antigen. A and B are co-dominant alleles, as a result, AB individuals express both antigens.

Possible blood types

Those are the six possible ways these alleles can be combined resulting in one of the four blood types [5]:

GenotypeBlood type
AAA
AOA
BBB
BOB
ABAB
OOO

Depending on the parent alleles, those are all possible combinations for the baby [5]:

Parent allelesAABBABOOAOBO
AAAAABAA, ABAOAA, AOAB, AO
BBABBBAB, BBBOAB, BOBB, BO
ABAA, ABAB, BBAA, BB, ABAO, BOAA, AO, BO, ABBB, BO, AB, AO
OOAOBOAO, BOOOAO, OOBO, OO
AOAA, AOAB, BOAA, AB, AO, BOAO, OOAA, AO, OOAO, BO, AB, OO
BOAO, ABBB, BOAB, AO, BB, BOBO, OOAB, AO, BO, OOBB, BO, OO

Blood type compatibility

The ABO blood type is based on the presence or absence of the A and B antigens on the red blood cells. People with the A blood type have only the A antigen, while people with the B blood type have only the B antigen. AB blood type has both A and B antigens, and O blood type has neither A nor B antigens.

By six months old, you have developed immunity against the antigens your red blood cells lack. People with the A blood type have antibodies against the B blood type, and people with the B blood type have antibodies against the A blood type. If you have type A blood, you cannot get type B blood because your body’s anti-B antibodies fight the B antigens in B blood.

AB positive blood (AB+) is considered the universal donor, and O negative blood (O-) is considered the universal recipient.

Blood type compatibilityO-O+B-B+A-A+AB-AB+
O- – – – – – – –
O+ – – – – – –
B-  – – – – –
B+ – – – –
A- – – – – – –
A+ – – – –
AB- – – – –
AB+
Table from [6]

ABO blood group and associated health risk

The ABO blood group system has been linked to several diseases, primarily cardiovascular problems [7]. The determination of ABO blood groups could serve in blood group individualized approaches towards health maintenance and prevention of diseases.

A study from 2020 published in Arteriosclerosis, Thrombosis, and Vascular Biology (AHA journals) showed that ABO blood groups were associated with 11 health and disease outcomes. ABO blood groups were primarily associated with cardiovascular outcomes. Individuals with blood group A and B were associated with hyperlipidemia, thrombosis, myocardial infarction and heart failure. Whereas, individuals with O blood groups were associated with hypertension.

Rhesus factor

The Rh factor is a protein that is found on the surface of red blood cells. If your red blood cells contain this protein, you are Rh positive. If your blood cells do not have this protein, you are Rh negative. Everyone inherits one Rh factor gene from each parent.

Depending on the parent’s Rh factor, the child could have the following Rh factor:

Parent Rh factorRh-/Rh-Rh+/Rh+Rh-/Rh+
Rh-/Rh-Rh-Rh+Rh-, Rh+ (Rh-/Rh+)
Rh+/Rh+Rh+Rh+Rh+, Rh+ (Rh-/Rh+)
Rh-/Rh+Rh-, Rh+ (Rh-/Rh+)Rh+, Rh+Rh-, Rh+, Rh+ (Rh-/Rh+)
 Table from [6]

Keep the following in mind:

  • Rh-/Rh- = Rh- factor
  • Rh-/Rh+ = Rh+ factor
  • Rh+/Rh+ = Rh+ factor

Rhesus factor compatibility

A medical problem can occur when a woman, who is Rh-, is pregnant with a Rh+ fetus [8]. The first child may have no difficulty, but subsequent similar pregnancies may produce severely anemic newborns. Exposure to the red blood cells of the first Rh+ fetus appears to protect the Rh- mother, thus potentially preventing her from developing antibodies that can cause brain damage in any subsequent Rh+ fetus. Damage to the fetal brain can occur as a result of the severe destruction of red blood cells. There are preventable measures available to prevent the severe effects of Rh incompatibility by transfusions to the fetus within the uterus. However, genetic counseling before conception is helpful so that the mother can receive Rh immunoglobulin immediately after her first and any subsequent pregnancies involving a Rh+ fetus.

This immunoglobulin effectively destroys the fetal red blood cells before the mother’s immune system is stimulated. Therefore, the mother avoids becoming actively immunized against the Rh antigen and will not produce antibodies that could attack the red blood cells of a future Rh+ fetus.

References

[1] World Health Organization (WHO). Blood safety and availability. Retrieved 13 September 2022 from https://www.who.int/news-room/fact-sheets/detail/blood-safety-and-availability

[2] Dean L. ABO Blood Group. 2012 Oct 1 [Updated 2015 Jul 27]. In: Pratt VM, Scott SA, Pirmohamed M, et al., editors. Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012- https://www.ncbi.nlm.nih.gov/books/NBK100894/

[3] David A-M et al. CHAPTER 26 – Introduction to haematology and transfusion science, Clinical Biochemistry: Metabolic and Clinical Aspects (Third Edition), Churchill Livingstone, 2014, Pages 497-514, ISBN 9780702051401, https://www.sciencedirect.com/science/article/pii/B9780702051401000262

[4] Banner Health. 4 Reasons You Should Know Your Blood Type. Retrieved 13 September 2022 from https://www.bannerhealth.com/healthcareblog/teach-me/4-reasons-you-should-know-your-blood-type

[5] The Tech Interactive. “What are all the possible blood types for any combination of parents?” Retrieved 13 September 2022 from https://www.thetech.org/ask-a-geneticist/ask199

[6] Baylor Scott & White Blood Center. Blood Type Genetics and Compatibility. Retrieved 13 September 2022 from https://www.bswhealth.com/patient-tools/blood-center/blood-type-genetics-and-compatibility

[7] Groot HE et al. Genetically Determined ABO Blood Group and its Associations With Health and Disease. Arterioscler Thromb Vasc Biol. 2020 Mar;40(3):830-838. doi: 10.1161/ATVBAHA.119.313658. Epub 2020 Jan 23. PMID: 31969017. https://www.ahajournals.org/doi/10.1161/ATVBAHA.119.313658

[8] Britannica. The genetics of human blood. Retrieved 13 September 2022 from https://www.britannica.com/science/human-genetics/The-genetics-of-human-blood

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