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Polymorphic genes, inheritance and blood groups
determination in animals and humans
Genetic determination of blood groups
Blood groups are generally understood all antigens on erythrocyte membranes, which are
capable of antibody production. These are proteins (receptors, enzymes or transport proteins),
glycoproteins or oligosaccharides. These antigens are usually called agglutinogens.
Antibodies (agglutinins) in the bloodstream occur either naturally or their production is
caused by the penetration of other blood group cells into the bloodstream.
Clustering of red blood cells in the presence of antibodies against a given antigen is known as
agglutination and is used for rapid determination of blood groups. This principle will be used
in practice.
Human blood groups
In humans, there are more than 30 blood group systems. Each system is controlled by one
gene locus or by two or more closely related homologous genes with low or none observable
recombination.
The most important systems are AB0, Rh and MNS.
AB0 system has four main blood groups: A, B, AB and 0.
This system is the oldest and most important. First was described by Austrian scientist and
physician Karl Landsteiner in 1901 (for this discovery got the Nobel Prize for Medicine in
1930). But Landsteiner described only three blood groups A, B and C (today 0).
Independently, the same conclusions got also Prof. MUDr. Jan Jansky in 1907. He identified
and classified all four blood groups, which marked I, II, III and IV.
Individuals with blood group A have on their red blood cells agglutinogen A and produce
anti-B antibodies, individuals with blood group B have agglutinogen B and produce anti-A
antibodies. Individuals with group AB have both agglutinogens and produce no antibodies.
Individuals with blood group 0 have no agglutinogens (there are only their precursor) and
produce antibodies against both agglutinogens.
Blood
group
A
B
AB
O
Agglutinogen Antibodies
A
B
A,B
-
anti-B
anti-A
anti-A, anti-B
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AB0 system is controlled by a single gene which is located on chromosome 9. This gene has
three alleles (IA, IB, i). Alleles and IA and IB are codominant (both alleles are responsible for
different phenotype), and the allele i is recessive to both IA and IB. IA allele encodes an
enzyme which produces agglutinogen A, IB allele produces agglutinogen B and recessive
allele i encodes a variant enzyme who has lost its enzymatic activity.
The representation of blood groups is variable in different populations. In the Czech Republic
it is following: A 45 %, 0 30-35 %, B 15-20 %, AB 5-7 %.
If different blood group is transfused from recipient to donor, a severe acute haemolytic
reaction with haemolysis, renal failure and shock can occur, resulting even in death.
Antibodies can be highly active and can attack blood cells and bind components of the
complement system to cause massive haemolysis of the transfused blood.
Rh system (named after macaque rhesus and its agglutination of human red blood cells) is
system in human-blood transfusion with currently 40 antigens, where 5 antigens are the most
important (C, D, E, c, e). The most significant is the D antigen and it is called “Rh factor”. If
this D antigen is present, the blood is called Rh+, otherwise the Rh-. The presence/absence of
antigen is determined by a single gene. Genotypes DD and Dd determine phenotype Rh+,
genotype dd determines phenotype Rh-.
The representation in Europe is following: 84 % Rh+ and 16 % Rh- (in Asia, percentage of
Rh+ is higher).
Systems AB0 and Rh are mentioned together, for example A+, ABRh system is associated with a haemolytic disease of the newborn (HDN). A pregnant woman
can make antibodies if her fetus has a blood group antigen that she does not have. This can
happen if some of the fetus blood cells pass into the mother's blood circulation (e.g. a small
fetomaternal haemorrhage at the time of childbirth or obstetric intervention), or sometimes
after a therapeutic blood transfusion. This can cause Rh disease or other forms of haemolytic
disease of the newborn in the current pregnancy and/or subsequent pregnancies. If a pregnant
woman is known to have anti-D antibodies, the Rh blood type of a fetus can be tested by
analysis of fetal DNA in maternal plasma to assess the risk to the fetus of Rh disease. One of
the major advances of twentieth century medicine was to prevent this disease by stopping the
formation of Anti-D antibodies by D negative mothers with an injectable medication called
Rho(D) immune globulin. Antibodies associated with some blood groups can cause severe
HDN, others can only cause mild HDN and others are not known to cause HDN.
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Dogs blood groups
Dogs have seven major blood group systems and these systems are summary called as a
system of DEA (Dog Erythrocyte Antigen): DEA 1 – 7. For each system with the exception of
a DEA 1, dog can be positive (red blood cells have the appropriate antigen) or negative
(antigen is not on red blood cells). Some of these antigens are present in almost all dogs (DEA
4 and 6 have 98 % of dogs), other antigens are very rare.
The most important is a system of DEA 1, which has two subsystems DEA 1.1 and DEA 1.2.
Dogs can be positive in one of these subsystems or negative in both, but can't be double
positive.
Dogs with DEA 1.1- could not get blood DEA 1.1+. There is a similar problem as with the Rh
system - sensitization and subsequent haemolysis with another transfusion.
Cats blood groups
Cats have three blood groups: A, B and AB.
Genotypes AA and Ab produce blood group A, genotype bb produce blood group B. Blood
group AB is rare (less than 1%) and its genetic determination has not yet been fully
elucidated. One possibility is that individual has genotype AB and some gene that allows
coexpression of both alleles. New studies suggest that there is another recessive allele aab,
which is recessive to the allele A and dominant to allele b (there is allele series A> aab > b).
The knowledge of cats blood groups is important for transfusion (the possibility of haemolytic
transfusion reaction) and for neonatal isoerythrolysis of kittens. If recipient with blood group
B get blood with blood group A, within minutes or hours destruction of erythrocytes blood
group A occurs. Neonatal isoerythrolysis is typical for kittens from mother with blood group
B and father with blood group A. Kittens with blood group A are not affected by antibodies
from the mothers during pregnancy (cats have placenta as natural barrier). The problem is
after birth, kittens (with blood group A) receive anti-A antibodies from colostrum, which
cause destruction of erythrocytes. The main prevention is to determine mothers and fathers
blood group before mating.
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Genetics of blood groups – examples
Humans
1. What blood groups are expected in offspring of parents with genotypes IAi and IBi?
2. What are the genotypes of parents, if father has blood group AB, mother B and their
children ¼ A, ¼ AB and ½ B?
3. Which of two men can be excluded as a father? Mother has blood group B, children 0,
first man has A and second has AB.
4. Parents are heterozygotes in blood groups B. What is the probability that their
firstborn son will inherit the group B? And what is the probability, if the firstborn
child is daughter?
5. Parents are heterozygotes in blood groups A. What is the probability that their two
children will inherit the group A?
6. Mother has blood group B and her child A. Mother said, that father of child is man
with blood group AB. Is this possible?
7. During one night in one hospital four children with blood groups A, B, AB and 0 were
born. Due to mistake of nurse we do not know which child was born to which mother.
Therefore the blood groups of all four pairs of parents were examined. First parents
have blood groups B x B, second have 0 x AB, third parents have groups A x B and
fourth pair have groups 0 x 0. Is it possible to determine which parents have which
children? If yes, which children belong to first parents, which to second parents, to
third and fourth parents?
8. What are the blood groups of men, which can't be fathers if we know blood groups of
mother and child: a) mother 0, child A, b) mother 0, child 0, c) mother A, child B, d)
mother AB, child B
Animals
1. A cat with blood group B has been mating with the tomcat with an unknown blood
group. Four kittens have blood group A and three blood group B. What are the
genotypes of parents and kittens?
2. A cat with blood group A has been mating with the tomcat (male) with blood group B.
What blood groups can have their kittens?
3. A cat with blood group AB had gradually kittens with two tomcats. All kittens from
the first cast had blood group A, kittens from the second cast had blood groups A, AB
or B. What blood groups had both tomcats and what are genotypes of parents and
offspring?
Elaborated: Ph.D., Doc. MVDr. Eva Bártová, Mgr. Petra Frolková
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