Inheritance of Blood Group System

Dr. Arvind Kumar

Introduction

  • Inheritance of Blood Group System is determined by the presence or absence of specific antigens on the surface of red blood cells (RBCs).
  • These antigens are genetically inherited from our parents.
    There are more than 30 blood group systems, but the most clinically important are:

    1. ABO blood group system

    2. Rhesus (Rh) factor system

These systems are important in blood transfusion, organ transplantation, and pregnancy.

ABO Blood Group System

Discovery

  • Discovered by Karl Landsteiner in 1901.

  • He found that mixing blood from different individuals sometimes caused clumping (agglutination), which led to the identification of A, B, AB, and O blood groups.

Genetic Basis

  • The ABO gene is located on chromosome number 9 (9q34).

  • This gene has three alleles: IA, IB, and i.

    • IA → produces A antigen on the red cell surface.

    • IB → produces B antigen on the red cell surface.

    • i → produces no antigen.

Dominance Relationship:

  • IA and IB are co-dominant, meaning both can be expressed together.

  • i is recessive, meaning it will be expressed only when both alleles are i (ii).

 

Molecular Basis of ABO System

  • The A and B antigens are complex sugar molecules (oligosaccharides) present on the surface of RBCs.

  • The H antigen acts as the base structure.

  • The A allele codes for an enzyme that adds N-acetylgalactosamine to the H antigen.

  • The B allele codes for an enzyme that adds galactose to the H antigen.

  • The O allele produces no enzyme, so the H antigen remains unchanged.

Thus:

Blood Type Antigen on RBC Added Sugar Molecule
A A antigen N-acetylgalactosamine
B B antigen Galactose
AB A and B antigens Both sugars
O No antigen None

 

Genotypes and Phenotypes

Blood Group Genotype Antigen on RBC Antibody in Plasma
A IAIA or IAi A antigen Anti-B
B IBIB or IBi B antigen Anti-A
AB IAIB A and B antigens None
O ii None Anti-A and Anti-B

 

Inheritance Pattern

Each individual inherits one allele from each parent.
Examples:

Parents’ Blood Groups Possible Blood Groups of Children
A × A A or O
A × B A, B, AB, or O
A × O A or O
B × O B or O
AB × O A or B
AB × AB A, B, or AB (no O)

 

Possible Blood Types

There are four main blood types based on ABO grouping:

  1. A type – has A antigen and anti-B antibodies

  2. B type – has B antigen and anti-A antibodies

  3. AB type – has both A and B antigens; no antibodies

  4. O type – has no antigens; both anti-A and anti-B antibodies

 

Blood Type Compatibility

Blood Transfusion Principles

  • Antigen-antibody reaction is the key.

  • If mismatched blood is transfused, agglutination (clumping) and hemolysis occur, which can be fatal.

Recipient’s Blood Type Can Receive Blood From Can Donate Blood To
A A, O A, AB
B B, O B, AB
AB A, B, AB, O AB (universal recipient)
O O only A, B, AB, O (universal donor)

Explanation:

  • O blood group has no antigens → safe for all recipients.

  • AB blood group has no antibodies → can receive from all groups.

 

ABO Blood Group and Associated Health Risks

Research studies show some correlations between blood groups and diseases:

Blood Group Health Associations
A Higher risk of stomach and pancreatic cancers, heart disease, and severe COVID-19 infection.
B Slightly increased risk of diabetes and blood clotting disorders.
AB Higher risk of cognitive impairment and thrombosis.
O Lower risk of heart disease and cancer, but higher risk of peptic ulcer due to H. pylori.

Note: These are associations, not direct causes.

Rhesus (Rh) Factor

  • The Rhesus (Rh) blood group system is one of the most important blood group systems after the ABO system.

  • It was discovered in 1940 by Karl Landsteiner and Alexander Wiener while studying Rhesus monkeys, hence the name Rhesus factor.

  • The Rh system is based on the presence or absence of a specific antigen known as the D antigen on the surface of red blood cells (RBCs).

Types of Rh Factor

  1. Rh Positive (Rh⁺)

    • If D antigen is present on RBCs.

    • Example: Blood type A⁺, B⁺, AB⁺, or O⁺.

  2. Rh Negative (Rh⁻)

    • If D antigen is absent on RBCs.

    • Example: Blood type A⁻, B⁻, AB⁻, or O⁻.

Approximately 85% of people are Rh positive, while 15% are Rh negative.

Genetic Basis

  • The Rh factor is controlled by a gene located on chromosome number 1.

  • The gene has two main alleles:

    • D (dominant) – produces the Rh (D) antigen.

    • d (recessive) – produces no antigen.

Genotypes and Phenotypes

Genotype Phenotype Description
DD Rh⁺ Homozygous dominant
Dd Rh⁺ Heterozygous
dd Rh⁻ Homozygous recessive

Inheritance:
Each person inherits one Rh gene from each parent.
Example:

  • If both parents are Rh⁺ (Dd), their child can be Rh⁺ or Rh⁻ depending on the combination of alleles.

 

Rhesus Factor and Blood Transfusion

Compatibility Rules:

Recipient’s Rh Type Can Receive Blood From Cannot Receive Blood From
Rh⁺ Rh⁺, Rh⁻ —
Rh⁻ Rh⁻ only Rh⁺ (causes reaction)

  • If an Rh⁻ person receives Rh⁺ blood, the immune system recognizes the D antigen as foreign and produces anti-D antibodies.

  • On second exposure, these antibodies attack and destroy the Rh⁺ red cells → causing hemolytic transfusion reaction.

 

Rhesus Factor and Pregnancy

Rh Incompatibility

  • Occurs when:

    • Mother → Rh⁻

    • Father → Rh⁺

    • Baby → Rh⁺ (inherits D antigen from the father)

During pregnancy or delivery, some fetal Rh⁺ blood may enter the mother’s bloodstream.
This causes the mother’s immune system to form anti-D antibodies (sensitization).

Effect on Future Pregnancies

  • In the first pregnancy, usually no problem occurs because antibodies form slowly.

  • In the next pregnancy with another Rh⁺ baby, the mother’s anti-D antibodies can cross the placenta and destroy the baby’s red blood cells.

This condition is called Hemolytic Disease of the Newborn (HDN) or Erythroblastosis Fetalis.

Symptoms of HDN

  • Severe anemia in the baby

  • Jaundice (yellow skin and eyes)

  • Enlarged liver and spleen

  • Swelling (edema)

  • In severe cases → stillbirth or death of the baby

Prevention

  1. Anti-D Immunoglobulin (Rho(D) Injection)

    • Given to Rh⁻ mothers within 72 hours after delivery of an Rh⁺ baby.

    • Also given after miscarriage, abortion, or ectopic pregnancy.

    • It destroys any Rh⁺ fetal cells in the mother’s blood before her immune system can react.

  2. Blood Typing During Pregnancy

    • Both parents’ blood groups are tested early in pregnancy to assess the risk.

  3. Monitoring

    • Antibody screening and fetal health checks (ultrasound, amniotic fluid tests) are done regularly if incompatibility is suspected.

 

Clinical Importance of Rh Factor

  1. Safe Blood Transfusion – prevents hemolytic reactions.

  2. Safe Pregnancy – avoids HDN by giving anti-D injection.

  3. Blood Donation and Organ Transplantation – ensures compatibility.

  4. Forensic Medicine – helps in parentage testing and identity verification.

Genetic Basis

  • Controlled by RhD gene on chromosome 1.

  • Two main alleles:

    • D (dominant) → produces D antigen (Rh⁺)

    • d (recessive) → no antigen (Rh⁻)

  • Genotypes:

    • DD or Dd → Rh⁺

    • dd → Rh⁻

Rhesus Factor Compatibility

Blood Transfusion

Recipient’s Rh Type Can Receive From
Rh⁺ Rh⁺, Rh⁻
Rh⁻ Only Rh⁻

If Rh⁻ person receives Rh⁺ blood → their immune system forms anti-D antibodies → causes hemolytic reaction on second exposure.

Rhesus Factor in Pregnancy (Hemolytic Disease of the Newborn)

  • Occurs when:

    • Mother = Rh⁻

    • Father = Rh⁺

    • Baby = Rh⁺

  • During childbirth, some Rh⁺ fetal blood may enter mother’s circulation.

  • Mother’s immune system forms anti-D antibodies.

  • In a second pregnancy with another Rh⁺ baby, these antibodies can cross the placenta and destroy fetal RBCs → causing Hemolytic Disease of the Newborn (HDN) or Erythroblastosis fetalis.

Symptoms in baby:

  • Jaundice

  • Anemia

  • Enlarged liver and spleen

  • In severe cases, stillbirth

Prevention:

  • Give anti-D immunoglobulin (Rho(D) injection) to Rh⁻ mothers within 72 hours after delivery of an Rh⁺ baby.

  • This prevents antibody formation.