inheritance and genetic of blood group
TRANSCRIPT
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The Blood Group Systems
Inheritance and GeneticsNawsherwan sadiq
2012-2013
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• The blood group you belong to depends on what you have inherited from your parents.
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• 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.
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Blood group AIf 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 BIf you belong to the blood group B, you have B antigens on the surface of your RBCs and A antibodies in your blood plasma.
AB0 blood grouping system
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Blood group ABIf 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 OIf 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.
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• 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.
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Inheritance of ABO Groups
Allele from the mother
Allele from the father
Genotype ofoffspring
Blood types ofoffspring
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
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ABO Typing
• Cell Group– Test Washed Cells With:– Monoclonal Anti-A– Monoclonal Anti-B– Inert control
• Agglutination is a positive result
• Reverse Group– Test plasma/serum with:– Known A1 cells– Known B cells– Known O cells– ? Known A2 cells
• Reactions may be weaker than cell group
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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
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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
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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
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Distribution of Rh(D) Types
Population Rh(D) pos Rh(D) neg
Caucasian 86% 14%
African-American
95% 5%
Oriental >99% <1%
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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
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ABO & Rh(D) 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
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Inheritance of ABO and Rh(D)
Mother
Group A AO
Rh(D) pos Dd
Father
Group B BO
Rh(D) pos Dd
Group A AO
Rh(D) pos Dd
Group B BO
Rh(D) pos Dd
Group O OO
Rh(D) neg dd
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• The ABO gene is autosomal (the gene is not on either sex chromosomes)
• The ABO gene locus is located on the chromosome 9.
• Each person has two copies of genes coding for their ABO blood group (one maternal and one paternal in origin)
• A and B blood groups are dominant over the O blood group
• A and B group genes are co-dominant
ABO inheritance and genetics
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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
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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
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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
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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
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Important Parts for Forensic Science
• Red Blood Cells—because of their importance in blood typing
• Serum—because of its’ importance in carrying antibodies
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• 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.
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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
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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
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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
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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)
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RBC Precursor Structure
Glucose
Galactose
N-acetylglucosamine
Galactose
Precursor Substance (stays the
same)
RBC
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Formation of the H antigen
Glucose
Galactose
N-acetylglucosamine
Galactose
H antigen
RBC
Fucose
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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
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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
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Formation of the A antigen
Glucose
Galactose
N-acetylglucosamine
Galactose
RBC
FucoseN-acetylgalactosamine
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Formation of the B antigen
Glucose
Galactose
N-acetylglucosamine
Galactose
RBC
FucoseGalactose
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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
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Group O Group A
Many H antigen sites
Fewer H antigen
sites
A
A A
AA
Most of the H antigen sites in a Group A individual have been
converted to the A antigen
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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
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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
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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
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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
Se gene (SeSe or Sese)
H antigen in secretions
A antigen
B antigen
se gene (sese) No antigens secreted in saliva or other
body fluids
and/or
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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
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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
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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 A1 antigen sites
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A1 and A2 Subgroups*Anti-A
antiseraAnti-A1 antisera
Anti-H lectin
ABO antibodies in serum
# of antigen sites per
RBC
A14+ 4+ 0 Anti-B 900 x103
A24+ 0 3+ Anti-B &
anti-A1
250 x103
*Adapted from Flynn, J. (1998). Essentials of Immunohematology
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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
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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
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ABO Blood Group:
ABO Antibodies
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Landsteiner’s Rule:
• Normal, Healthy individuals possess ABO antibodies to the ABO antigen absent from their RBCs
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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
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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”
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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.
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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
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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)
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ABO antibody facts
• Reactions phase: Room temperature• Complement can be activated with ABO
antibodies (mostly IgM, some IgG)• High titer: react strongly (4+)
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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
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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
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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
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AUTOSOMAL CHROMOSOME
Dad
Mom
The alleles for Blood group are in the same
place on the chromosome 9.
However the genes have a different code giving the different
blood group
A B
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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)
What do co-dominant genes mean?
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ParentAllele
A B O
A
B
O
Possible Blood group Genotypes
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ParentAllele
A B O
A AA AB AO
B AB BB BO
O AO BO OO
Possible Blood group Genotypes
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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 Group
Antigens on RBCs
Antibodies in Serum Genotypes
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
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The ABO Blood Group System
Laboratory Determination of the
ABO System
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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.
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• Illustration of the forward and reverse grouping reaction patterns of the ABO groups using a blood group tile
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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.
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Blood Group
Antigens Antibodies Can give blood to
Can receive
blood from
AB
A
B
O
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Blood Group
Antigens Antibodies Can give blood to
Can 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