CYTOGENETICS

Midterms #5: MULTIPLE ALLELES AND BLOOD GENETICS

PROF. AREL RELOX, RMT
APRIL 2, 2021
For updates and corrections → @mar4rii on Twitter

III. BLOOD GENETICS

OUTLINE ● Good example of multiple allelic gene
I. Mendel’s Principles - G. Blood types ● The human ABO gene is on chromosome 9
Review H. ABH Antigen ● Everyone has two copies of chromosome 9, so you have
A. Exceptions to Mendel’s I. RBC Precursor two ABO genes
Work Structure ● One copy is inherited from our mother, the other from our
II. Multiple Alleles IV. Antigens father.
III. Blood Genetics V. Antibodies
A. ABO Blood System VI. Blood Transfusion A. The ABO blood system
B. Alleles VII. Problems with Multiple ● This is controlled by a tri-allelic gene (3 Alleles)
C. Pheno vs. Geno Alleles ○ Allele IA produces antigen A
D. Dominant vs. VIII. Rh Blood Group System ○ Allele IB produces antigen B
Recessive IX. Blood Types and Rh Type ○ Allele i produces no antigen
E. Multiple Alleles Questions ○ I - isoagglutinogen (another term for antigen for
F. Determine genotype X. Stats blood type)
○ i - recessive (blood type O)
● It can generate 6 genotypes and 4 phenotypes
I. MENDEL’S PRINCIPLES - A Review ● The alleles control the production of antigens on the
surface of the red blood cells
● Inheritance of traits is determined by genes
● Two of the alleles are codominant to one another and both
● Genes are passed from parents to offspring
are dominant over the third (A and B)
● Alleles can be dominant or recessive
● In sexually reproducing organisms - each adult has two
B. Alleles
copies of each gene - one from each parent.
● There are three versions (called ‘alleles’) of this blood type
gene: A, B, and O
A. Exceptions to Mendel’s Work
● The person’s blood type is determined by which allele
● Some alleles are neither dominant nor recessive
he/she inherits from each parent
○ Codominant (Blood type A and B)
○ Can be expressed together
C. Pheno vs. Geno
● Many traits are controlled by multiple alleles or multiple
● The genetic makeup of an organism is called the
genes
“genotype”
● The “phenotype” is the visible properties of an organism
II. MULTIPLE ALLELES ● In this case, the A, B, and O allele combination in a person
● Homologous chromosomes has is their genotype
○ Chromosomes occur in pairs (homologous mean ● Their blood type is their phenotype
“same”)
■ Carry the same genes and occupy the D. Dominant vs. Recessive Genes
same location ● The “A” allele is dominant and so is the “B” allele
○ The different alleles of a gene occupy the same ● Together though, the “A” and “B” alleles are co-dominant
positions on each chromosome ○ Can be expressed together
● So far, each gene we have discussed has been made of ● The “O” allele is recessive
two possible alleles (dominant or recessive)
○ Ex. B = blue, b = yellow, R = red, r = white
E. Multiple Alleles
● However, it is possible to have several different allele
possibilities for one gene
● Multiple alleles is when there are more than two allele
possibilities for a gene
● Coat color in rabbits is determined by a single gene with 4
possible alleles

● AA - homozygous A
○ Phenotype: Blood type A
● BO - heterozygous B
○ Phenotype: Blood type B (O is recessive)

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 ■ Our body doesn't produce an antibody
F. Determining the Genotype against our own antigen (except for
● Human blood type is controlled by three alleles : IA, IB, and i autoimmune diseases)
● Alleles IA and IB are dominant over i ○ Universal recipient
● IA and IB are codominant ■ No antibodies will destroy or react upon
the donors antigen
○ Prioritize your same blood type when donating
Phenotype (blood type) Genotypes ● Blood Type O (recessive for A and B)
○ No antigens on the surface of the body
A IA IA or IA i ○ Anti A and Anti B antibodies in serum or plasma
● A allele codes for ○ Universal donor
enzyme ■ No antigen
glycosyltransferase ■ No reaction from antibodies of other
○ Specific blood types because absence of antigen
glycosyltransferase ■ Priority is Type O (Blood type O only
for different blood receive Type O)
types
● Modifies carbohydrate H. ABH Antigens
content of RBC antigen ● Results from the interaction of genes at three separate loci
● Can use A or O (ABO, Hh, and Se)
○ Produce specific glycosyltransferases that add
B IBIB or IBi sugars to a basic precursor substance
○ A, B, & H Ag are formed from the same basic
AB IAIB precursor material paragloboside or glycan
■ Basic precursor substance
O ii ■ If your gene or allele is A, it will code a
specific glycosyltransferase that adds a
sugar to the paragloboside
G. Blood Types
● The alleles we discussed “code” for blood type
● What they really “code” for is a specific enzyme
● That enzyme creates specific antigens on your RBC.

I. RBC Precursor Structure

● Blood type A
○ 2 possible genotypes: homozygous or
heterozygous A
○ Antigens on the surface of RBC is A antigen
○ Anti B antibody
● Antibodies of ABO are naturally occuring and expected
○ What you don’t have is your naturally occurring
antibody
○ Not naturally occurring means, since birth the
antibody is absent
■ You will only acquire this antibodies if
you’re exposed to the antigen
■ Ex. Exposure to COVID 19 patient
● Immune system produces
antibodies against covid 19 ● In the surface of the RBC, we have the precursor
● Not naturally occurring substance (paragloboside or glycan)
antibody (because it is ○ Composed of glucose, galactose,
acquired from exposure) n-acetylglucosamine, galactose
● Blood type B ● How does it add sugar?
○ 2 possible genotypes: homozygous or ○ Formation of Blood Type A
heterozygous B ■ Presence of A allele coding for a
○ Antigens on the surface of RBC is B antigen specific glycosyltransferase =
○ Naturally occurring, not expected: Anti A antibody n-acetylgalactosaminyl transferase
● Blood type AB ■ Which codes for the
○ Genotype: IAIB N-acetylgalactosamine (sugar added to
○ Antigens on the surface of RBC is both A and B the paragloboside)
(codominance) ○ Formation of Blood Type B
○ No Anti A and Anti B antibody
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 ■ Specific glycosyltransferase of B antigen V. ANTIBODIES
= D-galactosyl transferase ● Blood plasma is packed with proteins called antibodies.
■ Codes for galactose sugar (added to ○ Does not attack self antigen
paragloboside) ● The body produces a wide variety of antibodies that will
○ Formation of H antigen recognize and attack foreign molecules.
■ Can be homozygous dominant or ● A person’s plasma does not contain any antibodies that will
heterozygous dominant bind to molecules that are part of his or her own body.
■ Presence of H gene coding for a specific
glycosyltransferase = L-Fucosyl
Transferase Enzyme
■ Creates a sugar called Fucose (creates
the H antigen)
● What is the significance of H antigen to the formation of A
and B antigen?
○ Before Blood type A is formed, you should have H
antigen (to express A)
■ Needs H gene (which codes for
enzyme l-fucosyl transferase enzyme
which creates production of fucose)
● Formation of H antigen
○ Form A antigen
■ A gene (n-acetylgalactosaminyl
transferase creating
VI. BLOOD TRANSFUSIONS
n-acetylgalactosamine)
● It is important to carefully match the donor and recipient
■ Formation of Blood type A is only
blood types.
possible with the presence of Fucose
● If the donor’s blood cells have antigen that are different
● Absence will not produce type
from those of the recipient, antibodies in the recipient’s
A
blood recognize the donor blood as foreign.
● Bombay Phenotype “O”
○ Incompatibility cause adverse reaction
○ Bombay Phenotype “O”
● This triggers an immune response resulting in blood clotting
■ A gene codes for
or agglutination.
N-acetylgalactosaminyl transferase but
○ Leads to reduction of blood supply
no H gene
■ A is not expressed
■ Same goes with B gene without H gene
○ H antigen is a building block for the production of
antigens within ABO blood group

GENOTYPES PHENOTYPES ANTIBODY

● If recipient is Blood type B, receiving Blood type A
IA IA ; HH A Anti-B ○ Blood type B - Anti A antibody
○ Anti A will bind to the surface A antigen
IA IA Hh A Anti-B and destroy it (hemolysis)
○ Binding of antibodies will cause
IA hh “O” Anti-A, Anti-B, clumping leading to blood clot
Anti-H ○ Reduced blood supply
○ Cross matching should be performed
● Difference of Bombay Phenotype to Type O first
○ Blood type O still has H antigen
■ Recessive (absent) A and B antigen
○ Bombay Phenotype has no H antigen
■ Absent A and B antigen

IV. ANTIGENS
● An antigen is a protein (encoded from the right enzyme)
that “sits” on the surface of your RBC.
● There are 2 different blood antigens, A and B.
● If you have the A antigen, you have type A blood.
● If you have the B antigen, you have type B blood.

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 VII. PROBLEMS WITH MULTIPLE ALLELES ● Positive (+) allele is dominant to negative (-) allele
● Rh +: you have the protein | Rh-: you don’t
A. Problem 1: Multiple Alleles
● Show the cross between a mother who has a type O blood
and a father who has a type AB blood
● Genotypes:
○ IAi (2) IBi (2)
○ Ratio 1:1
● Phenotypes:
○ type A blood (2); type B blood(2)
○ 1:1
A. Rhesus Factor
● If a person has either two (+) genes for Rh or one (+) and
one (-) Rh gene, they will rest Rh (+)
● A person will be negative only if they have 2 (-).

B. Problem 2: Multiple Alleles

● Show the cross between a mother who is heterozygous for
type B blood and a father who is heterozygous for type A
blood ● One of the basic differences between ABO and Rh systems
● Genotypes: is that the Rh antibodies are not natural i.e. they are not
○ IAIB (1); IBi (1); IAi (1); ii (1) present at birth but are synthesised in Rh negative
○ ratio 1:1:1:1 persons in response to the presence of Rh-antigen.
● Phenotypes: ○ Depends on exposure
○ type AB (1); type B (1) type A (1); type O (1) ● Rh antigens are transmembrane proteins with loops
○ ratio 1:1:1:1 exposed at the surface of red blood cells.
● They appear to be used for the transport of carbon dioxide
and/or ammonia across the plasma membrane.

B. Rh Blood Group and Rh Incompatibility

● A person with Rh- blood does not have Rh antibodies
naturally in the blood plasma

C. Relative Abundance of Blood Types

C. The “Rh Issue”

● Mom = Rh (-)
● Baby #1 = Rh (+)

● Most abundant = Blood Type O

○ Can only receive type O

VIII. Rh BLOOD GROUP SYSTEM

● The Rhesus factor gets its name from experiments
conducted in 1937 by scientists Karl Landsteiner and
Alexander S. Weiner.
○ Karl Landsteiner discovered ABO blood group
system
● Involved Rabbits which when injected with the Rhesus
monkey’s red blood cells, produced an antibody – anti-Rh
(reacted also with most human red cells). ● Rh Significance
○ Different on humans ○ it is responsible for Hemolytic Disease of
○ Different Rh factors of monkey and humans Newborn (HDN)
○ Human uses D-antigen (for Rh antigen) ■ Other term: hydrops fetalis
● Most people (about 85%) have a positive Rh factor ■ Baby inherits Rh + blood from father and
○ Especially asians the mother is Rh - (baby has Rh +)
● Rh is expressed as either positive or negative. ■ Mother will reach by producing Anti Rh
● The Rh factor, like other antigens, is found on the surface of antibodies to attack the antigen of the
the red blood cells. fetus
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 ● Causing first born child to have
jaundice (because antigens of
baby were destroyed by
antibody of the mother)
■ If detected earlier, drugs can prevent
this scenario
● Second child will die because
mother has produces a lot of
antibody for the Rh + antigen
○ A+ donor is compatible with A+ recipient, and vice
versa

IX. BLOOD TYPES AND Rh TYPE QUESTION

● Example: A woman heterozygous for blood type A and
heterozygous for the rhesus allele, Rh+, has a child with a
man with type O blood who is Rh-. What is the probability
that their child will have blood type A, Rh+?
○ There will be a 50% chance.

ABO

Rh (D)

Genotype
● AO, Dd (2) 50% - heterozygous A, heterozygous Rh
positive
● OO, dd (2) 50% - Homozygous O, homozygous Rh
negative
Phenotype
● A, D positive = A+ → (2) 50%
● O, D negative = O- → (2) 50%
Ratio → 1:1

X. STATS

O+ 1 in 3 persons

O- 1 in 15 persons

A+ 1 in 3 persons

A- 1 in 16 persons

B+ 1 in 12 persons

B- 1 in 67 persons

AB+ 1 in 29 persons

AB- 1 in 167 persons