Genetics of blood groups

www.health.gov.mt/ nbts/bldgroup.htm

I. GENETICS of BLOOD GROUPS

™There are over 400 blood group antigens

™We will concentrate on two blood group systems:

1. ABO
2. Rhesus

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 Antigen-Antibody reaction

Antigen: Any foreign particle. It can also be protein or glycoprotein

-(sugar + protein) expressed on the surface of cells (RBCs).

Antibody: Glycoprotein generated by the immune system,

interacts with the antigen.

1. ABO BLOOD GROUP

™ Each of us has a unique blood group, either
¾ Group A, Group B, Group AB, or Group O.
™ This is determined by a reaction of the individual red blood cells
(RBCs) with specific antisera for each of the antigens (anti-A, anti-B).

¾ Group A individuals have the A antigen on the

surface of their RBCs
¾ Group B express the B antigen,

¾ Group AB have both A and B antigens, ¾

Group O have Neither antigens.

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 Antigens & Antibodies in the ABO System
™ There are two antigens (A & B antigens) and two antibodies
(anti-A & anti-B) that are responsible for the ABO types.

Blood Type Antigens on RBCs Antibodies in Serum

A A anti-B
B B anti-A
AB A+B none
O none anti-A + anti-B

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 Blood Type Antigens on RBCs Antibodies in Serum
A A anti-B
B B anti-A
AB A+B none
O none anti-A + anti-B

™ Type A people have the A antigen on the surface of their red cells
=> anti-A antibodies will NOT be produced because they would
cause the destruction of their own blood.

™ If B type blood is injected in Type A individual, anti-B

antibodies in plasma of TypeA ind. will recognize it as alien ->
agglutination/clumping of cells which are then destroyed in order to
cleanse the blood of alien protein.

www.biologymad.com/ Immunology/Immunology.htm 7

Blood Type Antigens on RBCs Antibodies in Serum

A A anti-B
B B anti-A
AB A+B none
O none anti-A + anti-B

™ Type O people do not produce A or B antigens.

¾ Therefore, their red cells will not be agglutinated by those with blood
groups A, B or AB.
¾ As a result, type O people are universal donors for transfusions. ¾ Note

however, that the serum of blood group O people COULD conceivably

agglutinate red cells. In practice this is a small problem owing to the dilution
effect.

™ Similarly, AB people do not make any A or B antibodies.

¾Their blood does not discriminate against any other ABO type. ¾

Therefore, they are universal recipients for transfusions.

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 ABO Gene
™ Located near the tip of the long arm (q) of chr. 9.

™ 3 major alleles identified i.e. IA, IB, i

™ 6possible genotypes and 4 possible phenotypes:

Genotype Blood Type (Group) Incidence in UK

IA IA or IA i (AA or AO) A 41.72%
IB IB or IB i (BB or BO) B 8.56%
I I (AB)
AB AB 3.04%
i i (OO) O 46.68%

™ IA and IB are Co-Dominant, whereas is i Recessive.

www.bh.rmit.edu.au/.../ resources/genetics4.htm 9

ABO Blood Groups

(Donor)
(Receiver) (Receiver) (Receiver)
(A Ag) (B Ag) (A & B Ag)

www.anselm.edu/.../ genbio/geneticsnot.html 10
Cont. ABO System

™ It is not possible to differentiate between AA and AO, or BB and

BO by using antisera.
™ This can be done by constructing a pedigree (‘family tree’) or
possibly from DNA analysis.

www.bh.rmit.edu.au/.../ resources/genetics1.htm 11

2. RHESUS BLOOD GROUP

™ Two main Rhesus phenotypes:
¾ Rhesus Positive & Rhesus Negative.
™ Determined by the reaction of individual’s RBCs with the antiRh
antibody.
¾ Rhesus positive individuals possess the Rh antigen on their red
cells.
¾ Rhesus negative people do not.

™ Rhesus gene complex: found on chr. 1 with two alleles for each of
three genes that are close together
-> C or c, E or e, and D or not D (usually expressed as d). ™ It
is the presence of D that is important.

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 Rhesus Genotypes & Phenotypes

GENOTYPE NOTATION UK FREQUENCY Rh PHENOTYPE

cde/cde rr 0.15 Negative
CDe/cde R1r 0.32
CDe/CDe R1R1 0.17
cDE/cde R2r 0.13 Positive
CDe/cDE R1R2 0.14
cDE/cDE R2R2 0.04
Others (rare) 0.05 Most positive

™In Western Europe, 85% of individuals are Rhesus Positive & nearly all
of the Orientals & American Indians.
™However, 30% of Basques from Northern Spain are Rhesus Negative.

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Why does the Rhesus factor matter?

It can lead to haemolytic disease of the newborn (HDN) or jaundice
•There is no problem if mother and foetus are both Rh+ or Rh-

•HDN arises due to Rh incompatibility.

•i.e mother is Rh- and baby is Rh+

•This is an acquired haemolytic anaemia

•Due to transplacental transfer of Anti-D antibodies from
mother to baby.

•During birth, small amounts of foetal blood leak into the mothers
circulation, through the placenta.
•If the foetus is Rh+ and mother is Rh-, the foetal cells (RBCs)
stimulate the production of anti-D antibody in the mother.
These antibodies cross back into the second Rh+foetus and cause
lysis of the RBCs of the second Rh+foetus.
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Cont. Rhesus factor

™There is usually little problem with the first born child

whose blood is Rh+.
™But the leakage of foetal blood atbirth causes a
marked sensitisation of the mother’s immune
system.
™Hence subsequent Rh+ pregnancies may result in
severe haemolytic anaemia of the child who will
need a blood transfusion shortly after (or even
before!) birth.

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http://www.infoplease.com/ce6/sci/A0841716.html

Rhesus Incompatibility

1. During childbirth, 2. Mother will begin to 3. If she has another

some of the baby’s Rh
positive blood can
escape via placental villi
into the blood stream of
the mother.
produce antibodies pregnancy with an Rh+
(anti-D) against the baby, these antibodies (a
baby’s Rh+ blood (has form of IgG which can cross
D antigen). placenta) will pass through
the placenta and may harm
the baby (has D Ag).

Treatment: An injection of anti-D antibody is given to the woman

immediately after the birth of the baby -> destroy any of the baby’s blood cells
that may have entered the woman’s bloodstream before they have a chance to
sensitize her (i.e. produce antibodies).
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 Blood Group
Testing

www.homehealth-uk.com/ medical/bloodgroup.htm;
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Procedure

1) Place 3 drops of blood separately on a clean glass slide.

2) Add 1 drop of anti-A antibody on first blood sample and
anti-B antibody on second blood sample and for the third
sample rhesus antibody or anti-D antibody.
3) Mix the blood and reagent using a clean stick (use a fresh
stick for each drop of blood). Spread each mixture evenly on
the slide over an area of 10-15mm diameter.
4) Leave the slide for 1 minutes at room temperature (22 °-
24°C). Then look for agglutination.
5) Record the results.

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 Results

1 2 3

1)Blood sample + Anti A antibody

2) Blood sample + Anti B antibody
3) Blood sample + Anti D antibody

There was clumping of RBCs in 1, and no clumping was

observed in 2 and 3. Therefore, the blood group is A ,and
Rh -ve.