The document discusses the inheritance and genetics of blood group systems, focusing on the ABO and Rh blood group systems. The key points are: 1) The ABO and Rh blood group systems are the most important for blood transfusions. The blood group you belong to depends on what antigens you inherited from your parents. 2) The ABO system involves A, B, and O blood types which are determined by the presence or absence of A and B antigens. The Rh system involves Rh+ and Rh- blood types determined by the presence or absence of the Rh antigen. 3) Incompatible blood groups can cause agglutination if mixed, so it is important to understand blood group inheritance and compatibility for safe blood transf

1. The Blood Group Systems
Inheritance and Genetics
Nawsherwan sadiq
2012-2013

2. •The blood group you belong to depends on
what you have inherited from your parents.

3. • There are more than 20 genetically determined
blood group systems known today
• The AB0 and Rhesus (Rh) systems are the
most important ones used for blood transfusions.
• Not all blood groups are compatible with each
other. Mixing incompatible blood groups leads to
blood clumping or agglutination, which is
dangerous for individuals.

4. AB0 blood grouping system
Blood group A
If you belong to the blood
group A, you have A
antigens on the surface of
your RBCs and B
antibodies in your blood
plasma.
Blood group B
If you belong to the blood
group B, you have B
antigens on the surface of
your RBCs and A
antibodies in your blood
plasma.

5. Blood group AB
If you belong to the blood group
AB, you have both A and B
antigens on the surface of your
RBCs and no A or B antibodies
at all in your blood plasma.
Blood group O
If you belong to the blood group O,
you have neither A or B antigens on
the surface of your RBCs but you have
both A and B antibodies in your blood
plasma.

6. • The "A“ and "B" antigens are also produced
by some other plants and microorganisms.
Thus, individuals who do not recognize one or
more of these antigens as "self" will produce
antibodies against the plant or microbial
antigens.
• These antibodies will also react with human
antigens of the same kind whether introduced
via a blood transfusion or a tissue graft.

7. Inheritance of ABO Groups
Allele from Allele from Genotype of Blood types of
the mother the father offspring offspring
A A AA A
A B AB AB
A O AO A
B A AB AB
B B BB B
B O BO B
O O OO O
7

8. ABO Typing
• Cell Group • Reverse Group
– Test Washed Cells – Test plasma/serum
With: with:
– Monoclonal Anti-A – Known A1 cells
– Known B cells
– Monoclonal Anti-B
– Known O cells
– Inert control
– ? Known A2 cells
• Agglutination is a • Reactions may be
positive result weaker than cell group
8

9. Significance of ABO Group
• ABO mismatched transfusions:
– Rare
– May be life threatening
– Can be caused by technical or clerical error
– Intravascular haemolysis
– More severe in group O patients
9

10. The Rh(D) Antigen
• RH is the most complex system, with
over 45 antigens
• Discovered in 1940 after work on
Rhesus monkeys
• Subsequently discovered to be
unrelated to monkeys
• RH gene located on short arm of
chromosome 1
10

11. Simple Genetics of Rh(D)
• 86% of caucasians are Rh(D) pos
• The antigen d has not been found
• The d gene is recessive:
– Dd, dD, DD, persons are Rh(D) pos
– Only dd persons are Rh(D) neg
11

12. Distribution of Rh(D) Types
Population Rh(D) pos Rh(D) neg
Caucasian 86% 14%
African- 95% 5%
American
Oriental >99% <1%
12

13. Significance of Rh(D)
• 80% of Rh(D) neg persons exposed to Rh(D) pos
blood will develop anti-D
• Anti-D can also be stimulated by pregnancy with
an Rh(D) positive baby
– Sensitisation can be prevented by the use of anti-D
immunoglobulin, antenatally and post natally
• Rh(D) neg females of childbearing potential
should never be given Rh(D) positive blood
products
13

14. Inheritance
• ABO & RH genes are not linked
• ABO & Rh(D) type are inherited
independently
For example:
An A Rh(D) pos mother
and a B Rh(D) pos father
could have an O Rh(D) neg child
ABO & Rh(D) 14

15. Inheritance of ABO and Rh(D)
Mother Father
Group A AO Group B BO
Rh(D) pos Dd Rh(D) pos Dd
Group A AO Group B BO Group O OO
Rh(D) pos Dd Rh(D) pos Dd Rh(D) neg dd
15

16. ABO inheritance and genetics
• The ABO gene is autosomal (the gene is not on either sex
chromosomes)
• The ABO gene locus is located on the chromosome 9.
• A and B blood groups are dominant over the O blood group
• A and B group genes are co-dominant
• Each person has two copies of genes coding for their ABO blood
group (one maternal and one paternal in origin)

17. Principles of Heredity
• Antigens and enzymes are genetically controlled
– Genes: responsible for transfer of hereditable material
– Genes are found on chromosomes, which are found in the
nucleus of every cell
• Human Cells contain 46 chromosomes with the
exception of the egg and sperm, which contain only
23.
– 23 of these chromosomes are inherited from mother
– 23 of these chromosomes are inherited from father

18. Genes Come in Pairs
• The position a gene occupies on a chromosome is called a
locus.
• Genes for the same trait are located at the same locus on
both the mother and the father’s chromosomes.
• Alternative forms of genes that influence a given
characteristic are called alleles.
– Father: allele for brown eyes
– Mother: allele for blue eyes

19. Blood Types are Genetic
• A and B Blood Types are Dominant
– Dominant: Characteristic is shown
• Blood Type O is Recessive
– Recessive: Characteristic is hidden
– Recessive characteristics only appear when both alleles
are recessive
• Homozygous recessive OO

20. Phenotype V. Genotype
• Phenotype: individual’s outward characteristics
• Genotype: individual’s pair of allele genes together
• Example:
– Phenotype Genotype
Type B Blood Could be BO or
BB depending
on parents

21. Important Parts for Forensic Science
• Red Blood Cells—because of their importance in
blood typing
• Serum—because of its’ importance in carrying
antibodies

22. • The term serology refers to a broad scope of
laboratory tests that use specific antigen and serum
antibody reactions.
• Blood typing falls into this category.

23. ABO and H Antigen Genetics
• Genes at three separate loci control the
occurrence and location of ABO antigens
• The presence or absence of the A, B, and H
antigens is controlled by the H and ABO
genes

24. Location
• The presence or absence of the ABH
antigens on the red blood cell membrane is
controlled by the H gene
• The presence or absence of the ABH
antigens in secretions is indirectly
controlled by the Se gene

25. ABO Antigen Genetics
• H gene – H and h alleles (h is an amorph)
• Se gene – Se and se alleles (se is an
amorph)
• ABO genes – A, B and O alleles

26. H Antigen
• The H gene codes for an enzyme that adds
the sugar fucose to the terminal sugar of a
precursor substance (PS)
• The precursor substance (proteins and
lipids) is formed on an oligosaccharide
chain (the basic structure)

27. RBC Precursor Structure
RBC
Glucose
Galactose
Precursor
Substance
(stays the N-acetylglucosamine
same)
Galactose

28. Formation of the H antigen
RBC
Glucose
H antigen Galactose
N-acetylglucosamine
Galactose
Fucose

29. H antigen
• The H antigen is the foundation upon which
A and B antigens are built
• A and B genes code for enzymes that add an
immunodominant sugar to the H antigen
– Immunodominant sugars are present at the
terminal ends of the chains and confer the ABO
antigen specificity

30. A and B Antigen
• The ―A‖ gene codes for an enzyme (transferase)
that adds N-acetylgalactosamine to the terminal
sugar of the H antigen
– N-acetylgalactosaminyltransferase
• The ―B‖ gene codes for an enzyme that adds D-
galactose to the terminal sugar of the H antigen
– D-galactosyltransferase

31. Formation of the A antigen
RBC
Glucose
Galactose
N-acetylglucosamine
Galactose
N-acetylgalactosamine
Fucose

32. Formation of the B antigen
RBC
Glucose
Galactose
N-acetylglucosamine
Galactose
Galactose
Fucose

33. Genetics
• The H antigen is found on the RBC when
you have the Hh or HH genotype, but NOT
from the hh genotype
• The A antigen is found on the RBC when
you have the Hh, HH, and A/A, A/O, or
A/B genotypes
• The B antigen is found on the RBC when
you have the Hh, HH, and B/B, B/O, or A/B
genotypes

34. A A
A A
Group O Group A
Many H Fewer A
antigen sites H antigen
sites
Most of the H antigen sites in a
Group A individual have been
converted to the A antigen

35. ABO Antigens in Secretions
• Secretions include body fluids like plasma,
saliva, synovial fluid, etc
• Blood Group Substances are soluble
antigens (A, B, and H) that can be found in
the secretions. This is controlled by the H
and Se genes

36. Secretor Status
• The secretor gene consists of 2 alleles (Se
and se)
• The Se gene is responsible for the
expression of the H antigen on glycoprotein
structures located in body secretions
• If the Se allele is inherited as SeSe or Sese,
the person is called a ―secretor‖
– 80% of the population are secretors

37. Secretors
• Secretors express soluble forms of the H
antigen in secretions that can then be
converted to A or B antigens (by the
transferases)
• Individuals who inherit the sese gene are
called ―nonsecretors‖
– The se allele is an amorph (nothing expressed)
– sese individuals do not convert antigen
precursors to H antigen and has neither soluble
H antigen nor soluble A or B antigens in body
fluids

38. Secretor Status Summary
• The Se gene codes for the presence of the H
antigen in secretions, therefore the presence
of A and/or B antigens in the secretions is
contingent on the inheritance of the Se gene
and the H gene A antigen
Se gene (SeSe H antigen in and/or
or Sese) secretions B antigen
se gene (sese) No antigens secreted
in saliva or other
body fluids

39. ABO Subgroups
• ABO subgroups differ in the amount of antigen
present on the red blood cell membrane
– Subgroups have less antigen
• Subgroups are the result of less effective enzymes.
They are not as efficient in converting H antigens
to A or B antigens (fewer antigens are present on
the RBC)
• Subgroups of A are more common than subgroups
of B

40. Subgroups of A
• The 2 principle subgroups of A are: A1 and
A2
– Both react strongly with reagent anti-A
– To distinguish A1 from A2 red cells, the lectin
Dolichos biflorus is used (anti-A1)
– 80% of group A or AB individuals are
subgroup A1
– 20% are A2 and A2B

41. A2 Phenotype
• Why is the A2 phenotype important?
– A2 and A2B individuals may produce an anti-A1
– This may cause discrepancies when a
crossmatch is done (incompatibility)
• What’s the difference between the A1 and
A2 antigen?
– It’s quantitative
– The A2 gene doesn’t convert the H to A very
well
– The result is fewer A2 antigen sites compared to
the many A antigen sites

42. A1 and A2 Subgroups*
Anti-A Anti-A1 Anti-H ABO # of
antisera antisera lectin antibodies antigen
in serum sites per
RBC
A1 4+ 4+ 0 Anti-B 900 x103
A2 4+ 0 3+ Anti-B & 250 x103
anti-A1
*Adapted from Flynn, J. (1998). Essentials of Immunohematology

43. Other A subgroups
• There are other additional subgroups of A
– Aint (intermediate), A3, Ax, Am, Aend, Ael, Abantu
• A3 red cells cause mixed field
agglutination when polyclonal anti-A or
anti-A,B is used
• Mixed field agglutination appears as small
agglutinates with a background of
unagglutinated RBCs
• They may contain anti-A1

44. B Subgroups
• B subgroups occur less than A subgroups
• B subgroups are differentiated by the type
of reaction with anti-B, anti-A,B, and anti-H
• B3, Bx, Bm, and Bel

45. ABO Blood Group:
ABO Antibodies

46. Landsteiner’s Rule:
• Normal, Healthy
individuals possess
ABO antibodies to
the ABO antigen
absent from their
RBCs

47. Blood Group Systems
• Most blood group systems (ABO and
others) are made up of:
– An antigen on a red cell and the absence of it’s
corresponding antibody in the serum (if you’re
A, you don’t have anti-A)
• If you do NOT have a particular antigen on
your red cells then it is possible (when
exposed to foreign RBCs) to illicit an
immune response that results in the
production of the antibody specific for the
missing antigen

48. ABO
• Remember:
– The ABO Blood Group System does NOT
require the presence of a foreign red blood cell
for the production of ABO antibodies
– ABO antibodies are ―non-red blood cell
stimulated‖ probably from environmental
exposure and are referred to as ―expected
antibodies‖

49. Anti-A1
• Group O and B individuals contain anti-A
in their serum
• However, the anti-A can be separated into
different components: anti-A and anti-A1
• Anti-A1 only agglutinates the A1 antigen,
not the A2 antigen
• There is no anti-A2.

50. Anti-A,B
• Found in the serum of group O individuals
• Reacts with A, B, and AB cells
• Predominately IgG, with small portions
being IgM
• Anti-A,B is one antibody, it is not a mixture
of anti-A and anti-B antibodies

51. ABO antibodies
• IgM is the predominant antibody in Group
A and Group B individuals
– Anti-A
– Anti-B
• IgG (with some IgM) is the predominant
antibody in Group O individuals
– Anti-A,B (with some anti-A and anti-B)

52. ABO antibody facts
• Reactions phase: Room temperature
• Complement can be activated with ABO
antibodies (mostly IgM, some IgG)
• High titer: react strongly (4+)

53. ABO Antibodies
• Usually present within the first 3-6 months
of life
• Stable by ages 5-6 years
• Decline in older age
• Newborns may passively acquire maternal
antibodies (IgG crosses placenta)
– Reverse grouping (with serum) should not be
performed on newborns or cord blood

54. Paternity Tests
• No blood group can be present in a child without
being present in one of the parents
• Paternity tests can be resolved in this way unless
disputed fathers have the same blood type
• Paternity tests can also be determined by using DNA
testing

55. Blood as Evidence
• Blood typing not so useful anymore because of
DNA technology
• Scientists can now characterize biological evidence
by selecting regions of our DNA

56. AUTOSOMAL
CHROMOSOME
The alleles for Blood
group are in the same
A place on the B
chromosome 9. However
the genes have a
different code giving the
different blood group Dad
Mom

57. What do co-dominant genes mean?
This meant that if a person inherited one A group gene and one
B group gene their red cells would possess both the A and B
blood group antigens.
These alleles were termed A ( which produced the A antigen ),
B (which produced the B antigen) and O (which was "non
functional"and produced no A or B antigen)

58. Possible Blood group Genotypes
Parent A B O
Allele
A
B
O

59. Possible Blood group Genotypes
Parent A B O
Allele
A AA AB AO
B AB BB BO
O AO BO OO

60. The ABO blood groups
• The most important in assuring a safe blood transfusion.
• The table shows the four ABO phenotypes ("blood groups") present
in the human population and the genotypes that give rise to them.
Blood Antigens
Antibodies in Serum Genotypes
Group on RBCs
A A Anti-B AA or AO
B B Anti-A BB or BO
AB A and B Neither AB
O Neither Anti-A and anti-B OO

61. The ABO Blood Group System
Laboratory Determination of the
ABO System

62. Several methods for testing the ABO group of an
individual exist. The most common method is:
Serology: This is a direct detection of the ABO
antigens. It is the main method used in blood
transfusion centres and hospital blood banks.
This form of testing involves two components:
a) Antibodies that are specific at detecting a
particular ABO antigen on RBCs.
b) Cells that are of a known ABO group that
are agglutinated by the naturally occurring
antibodies in the person's serum.

63. • Illustration of the forward and reverse
grouping reaction patterns of the ABO
groups using a blood group tile

64. When RBCs carrying one or both antigens are exposed to the
corresponding antibodies, they agglutinate; that is, clump
together. People usually have antibodies against those red cell
antigens that they lack.
Human RBC before (left) and after (right) adding serum
containing anti-A antibodies. The agglutination reaction
reveals the presence of the A antigen on the surface of the
cells.

65. Blood Antigens Antibodies Can give Can
Group blood to receive
blood from
AB
A
B
O

66. Blood Antigens Antibodies Can give Can
Group blood to receive
blood from
AB A and B None AB AB, A, B, O
A A B A and AB A and O
B B A B and AB B and O
O None A and B AB, A, B, O O