Case 2- O Blood Type

Question 1

Evolutionary Pathways to Disease and/or Health

IMPORTANT

Answer 1

• An evolutionary matched environment.
• An evolutionary mismatched or novel environment.
• Outcomes of demographic history.
• Outcomes of cultural history. • Outcome of evolutionary constraints.
• Sexual selection and “sexual”competition and their
consequences.
• Life-history and/or developmental associated factors.
• Antagonistic pleiotropy.
• A harmful allele when homozygous is maintained by heterozygote
advantage.
• Effects of deleterious allele does not become apparent until after reproductive age.
• Spontaneous mutations for a deleterious gene defect replace alleles eliminated by selection.
• Exaptation.
• Excessive and uncontrolled defense mechanisms.
• Fighting the evolutionary arms race with microbes.

Question 2

Three relevant histories in systematic evolutionary framework
IMPORTANT

Answer 2

• #1: History of the complaint. • #2: Developmental history of the person.
• #3: Evolutionary history of the person and
their ancestors

Question 3

Human blood types

Answer 3

• A blood type (also called a blood group) is a classification of blood based on the presence or absence of inherited antigenic substances on the surface of red blood cells (RBCs).
• These antigens may be proteins, carbohydrates, glycoproteins, or glycolipids, depending on the blood group system.
• Blood types are inherited and represent contributions from both parents.
• A total of 30 human blood group systems are now recognized by the International Society of Blood Transfusion.

Question 4

ABO system

Answer 4

• The ABO system is the most important blood-group system in determining appropriate donors and recipients for human-blood transfusions.
• ABO is transmitted through monogenic inheritance.

Question 5

Mendelian Monogenic Inheritance Homozygous vs heterozygous

Answer 5

• Homozygous: the pair of alleles at a locus are identical.
• Heterozygous: the pair of alleles at a locus are different.
• A population of organisms within a species may include multiple alleles at the locus among various individuals.
• Allelic variation at a locus is measurable as the number of different alleles present, or the proportion of heterozygotes at that locus in the population

Question 6

Heterozygous dominant, recessive, co-dominant, & incomplete dominant genes in monogenic Mendelian genetics

Answer 6

• The allele that masks the other allele is called be
dominant.
• The allele that is masked is called recessive.
• When both alleles (e.g., blood type AB) are fully expressed they are co-dominant.
• Two different alleles are expressed as an intermediate between the two, is an example of
incomplete-dominance

Question 7

Incomplete dominance

Answer 7

• A heterozygous condition in which both alleles at a gene locus are partially expressed, often producing an intermediate phenotype
• Incomplete dominance is sometimes called partial dominance or intermediate dominance

Question 8

Mendelian Monogenic Inheritance Dominant Allele for red color of flower petal Recessive Allele for white color of flower petal Heterozygous are red

Answer 8

Gametes D (red) d (white)
D (red) DD
(red phenotype)
Dd
(red phenotype)
d (white) Dd
(red phenotype)
dd
(white phenotype)
CHECK DIAGRAM

Question 9

Mendelian Monogenic Inheritance Incomplete-dominant allele for red color of flower petal Incomplete-dominant allele for white color of flower petal Heterozygous are pink which is intermediate

Answer 9

Gametes D (red) d (white)
D (red) DD
(red phenotype)
Dd
(pink phenotype)
d (white) Dd
(pink phenotype)
dd
(white phenotype
CHECK DIAGRAM

Question 10

Mendelian Monogenic Inheritance Co-dominant Allele for A Blood Type Co-dominant Allele for B Blood Type Heterozygous fully expresses both A and B

Answer 10

Gametes A B
A AA
(A phenotype)
AB
(AB phenotype)
B AB
(AB phenotype)
BB
(B phenotype)

Check diagram

Question 11

ABO system

Answer 11

• Humans may have the same blood type phenotype (characteristic) but different genotypes (gene sequences)
• Three blood type alleles: A, B, & O
• Each human has two of these alleles
• A or B are each dominant over O which is recessive, but
neither A or B are dominant over each other
• Six possible genotypes: AA, AO, BB, BO, AB, OO
• Four blood types/phenotypes: A, B, AB, & O
• AA genotype: phenotype A
• BB genotype: phenotype B
• AB genotype: phenotype AB (universal recipient)
• AO genotype: phenotype A
• BO genotype: phenotype B
• OO genotype: phenotype O (universal donor)
• Depending on the person’s blood type, they may develop anti-A antibodies, anti-B antibodies, or no antibodies.
• Anti-O antibodies are NOT formed by humans.
• Persons with the genotype AA, AO, or OO will form anti-B antibodies if they are exposed to blood from a person with a BB, AB, or BO genotype, causing them to rejection the blood.
• Persons with the genotype BB, BO, or OO will form anti-A antibodies if they are exposed to blood from a person with a AA, AB, or AO genotype, causing them to rejection the blood.
• Persons with genotype OO will form both anti-A and anti-B antibodies when exposed to both A and B alleles
• Persons with genotype AB form no antibodies

Question 12

AB genotype is universal recipient

Answer 12

• A person with AB genotype is not capable of making anti-A or anti-B antibodies and can receive blood from any of the genotypes (i.e. AA, BB, AB, AO, BO, OO).
• People with AB genotype (AB phenotype) are universal recipients

Question 13

OO genotype is universal donor

Answer 13

• A person with OO genotype can make both anti-A or anti-B antibodies and therefore can NOT receive blood from the AA, BB, AB, AO, or BO genotypes because they will reject the blood
• A person with OO genotype can ONLY receive blood from a person with the OO genotype.
• People with OO genotype (O phenotype) are universal donors, because antibodies are not formed against O blood type by people with A, B, AB, or O blood types.

Question 14

Blood types in the USA Data from Stanford Blood Center

Answer 14

• Type A = 42%
• Type B = 10%
• Type AB = 4% (universal recipient)
• Type O = 44% (universal donor)

Question 15

Acute hemolytic reaction from rejection of blood transfusion because of ABO blood type mismatch

Answer 15

• Type O blood recipient will reject any blood type (A, B, & AB) other than Type O blood
• Type B blood recipient will reject blood types A & AB
• Type A blood recipient will reject blood types B & AB
• Type AB blood recipient will accept all blood types (= universal recipient)

Question 16

Human blood transfusions

Answer 16

• Use of human blood transfusions is relatively recent in human history.
• In relationship to blood transfusions, the disadvantage that people with Type O blood phenotypes have and the advantage that Type AB blood phenotypes have are recent in human history and are not traits that have been influenced by selection based on ability to receive life saving blood transfusions.
Acute hemolytic reaction from rejection of blood transfusion because of ABO blood type mismatch

Question 17

Maternal exposure to fetal RBCs during pregnancy

Answer 17

• A small number of fetal RBCs cross the placenta and enter the mom’s blood during the 2nd and 3rd trimesters

Question 18

Maternal-fetal ABO blood group incompatibility

Answer 18

• Humans may be blood group A, B, AB, or O
• Group O is universal donor
• Group AB is universal recipient
• If mom is blood group O conceives a fetus
who is blood group A or blood group B, a small amount of fetal blood cells can leak into the maternal blood circulation
• The group O mom may develop anti-A and/or anti-B IgG antibodies to these fetal blood type antigens
• These maternal anti-A or anti-B IgG antibodies can then pass through the placenta into the fetal circulation and cause destruction of fetal RBCs which can result in reduced RBCs and elevated bilirubin
• ABO maternal-fetal blood group incompatibility typically results in significantly less severe effects on the fetus/infant compared to Rh incompatibility

Question 19

Bilirubin

Answer 19

• Yellow breakdown product of hemoglobin

* When there is an abnormally high breakdown of red blood cells, the blood bilirubin level rises

Question 20

Case 2: Adult male from Chumash Indian tribe with O blood type in emergent need of blood transfusion

Answer 20

• This 30 year old Chumash Indian male was injured in a car accident and arrives by ambulance to the emergency room of a small hospital in California.
• Due to multiple lacerations, he has lost a fair amount of blood and his blood pressure is 40/90 which is dangerously low.
• He needs a blood transfusion emergently.
• He is O type (O phenotype) blood.
• Unfortunately, there is no O type blood available in
this small community hospital.

Question 21

Blood types

Answer 21

• The only blood available was A, AB, and B blood types (phenotypes).
• This Native American Chumash male is O blood type (O phenotype) and can only receive O blood type.
• Chumash Indian ancestral distribution is along the coast in southern California.

Question 22

Why was O type/phenotype

blood in low supply?

Answer 22

• All three blood type alleles (A, B, & O) are present in contemporary California human populations which are made up predominantly of people whose ancestors originated from Latin America, Europe, Asia, Africa, and Oceania in addition to a small percentage of Native California Indians
• A & B are dominant
• O is recessive
• Blood type O can be given to any ABO blood type
recipient, hence it can be used up quickly causing the available supply of type O blood to be less at this community hospital.

Question 23

Human blood type alleles

Answer 23

• Three blood type alleles: A, B, & O
• Each human has two of these alleles
• A or B are each dominant over O which is
recessive, but neither A or B are dominant over each other
• When both A and B alleles (blood type AB) occur together they are co-dominant

Question 24

Mendelian monogenic inheritance with full expression of two equally dominant alleles, A and B, for blood type Both parents are heterozygous for A & B (AB) One offspring is A blood type/phenotype One offspring is B blood type/phenotype Two offspring are AB blood type/phenotype

Answer 24

Alleles A B
A AA genotype
A phenotype
AB genotype
AB phenotype
B AB genotype
AB phenotype
BB genotype
B phenotype
CHECK DIAGRAM

Question 25

Which genotypes contain an O allele?

Answer 25

* BO * AO * OO

Question 26

Mendelian Monogenic inheritance with one dominant and one recessive allele: B (dominant) & O (recessive) blood type alleles One parent is homozygous for B (BB) One parent is heterozygous for B & O (BO) All offspring have B blood type/phenotype

Answer 26

``` Alleles B O B BB genotype B phenotype BO genotype B phenotype B BB genotype B phenotype BO genotype B phenotype CHECK DIAGRAM ```

Question 27

Influence of blood type/phenotype expression by interaction of two dominant alleles (A & B) with one recessive allele (O)

Answer 27

* Both A allele and B allele mask the recessive O allele so the frequency of O blood type/phenotype in the contemporary California human population is much lower that the O allele frequency in the population. * O blood type is the universal donor and can be received by any ABO blood type * These features contribute to the relatively low supply of O blood type/phenotype in California today.

Question 28

O Blood type

Answer 28

The supply of donor blood is further limited for people with O blood type/phenotype because they are universal donors and can only receive O type blood

Question 29

What genotype(s) generate(s) a blood phenotype O?

Answer 29

• OO genotype generates a blood phenotype O

Question 30

What parental genotype(s) generate a blood phenotype O in all offspring?

Answer 30

• Both parents need to be homozygous for OO for all offspring to be genotype OO and O blood type/phenotype.

Question 31

Chumash Indian patient outcome

Answer 31

* Because no O type blood was available, this male was immediately given fluids to maintain his blood pressure. * Soon after his arrival into the ER, two of his sisters arrived and both had their blood immediately typed and both were O type/phenotype. * Blood was donated at that time from his sisters and he was given a transfusion of fresh O type/phenotype blood. * He recovered from his injuries and was discharged to go home three days later.

Question 32

Why is this Native American O blood type/phenotype and OO genotype?

Answer 32

Distribution of O blood phenotype | in native populations around the world with yellow being the lowest and blue being the highest

Question 33

Human migration to the Americas

Answer 33

* At least 20,000 years ago the migration into the Americas occurred. * One or more migrations by relatively small groups of Siberian humans over the landmass called Beringia which connected present day Siberia and Alaska between 20,000-8,000 years ago because of the fallen ocean level during the last glacial period. * As the North American glaciers began to melt and recede about 20,000 years ago, the way for southward migration was opened and Homo sapiens reached southern South America as early as 14,000 years ago.

Question 34

Native American founder population

Answer 34

* Population bottlenecks from migration of small groups from the original population have resulted in founder effects which have caused a high level of genetic homogeneity in Native Americans in North America, Mexico, Central America, and South America. * Some scientists suggest that the original founder population in the Americas may have been 70 or fewer individuals. * Amerindians are found to mostly have blood phenotype O (genotype OO); this high frequency of blood type O is thought to be due to a genetic bottleneck that generated a founder effect.

Question 35

Human migration to the Americas

Answer 35

• An example of the low genetic diversity in Native Americans is the fact that nearly all have blood phenotype O/genotype OO (especially in western USA, Mexico, Central American and South American Indians), with a very low frequency of blood type A and blood type B.

Question 36

Bottleneck

Answer 36

a dramatic reduction in population size by due to migration of a small population from the original population in Asia.

Question 37

Founder Effect

Answer 37

The principle that the founders of a small new population generated by a bottleneck, carry only a fraction of the total genetic variation in the original larger source population.

Question 38

Bottlenecks, founder effects, and subsequent population growth

Answer 38

* Bottleneck generated a small population compared to original source population size. * This small population tended to be influenced by genetic drift but could have also be influenced by natural selection, however, there was not likely a significant selective force for the O allele over the A or B alleles for the populations as they migrated into the Americas.

Question 39

Genetic drift

Answer 39

* In large populations, in the absence of selection, allele frequencies tend to change very slowly over generations. * In small populations, in the absence of selection, the stochastic nature of reproductive processes means that alleles may be lost (0% frequency in the population) or fixed (100% frequency in the population) within a few generations.

Question 40

Blood phenotype B

Answer 40

* Blood group B is in highest frequency in northern India and Central Asia * Believed to have been entirely absent from Native American and Australian Aboriginal populations prior to the arrival of Europeans. * Today, frequency of type B blood allele in Native Americans is 4%, even though Type B blood allele is significantly more common in the Asian population from where the Native Americans migrated.

Question 41

Blood phenotype B has some protection against cholera

Answer 41

• It is believed that the high frequency of blood phenotype B in northern India along the Ganges River basin is because it was positively selected for since of it offers protection against cholera diarrhea.

Question 42

O allele and cholera susceptibility

Answer 42

* O allele is more susceptible to severe forms of cholera infections * Swerdlow et al. J Infect Dis 1994, 170(2):468-472. Severe life-threatening cholera associated with blood group O in Peru: implications for the Latin American epidemic. * Cholera was not present in the Americas in pre-Columbian times. * The higher rates of the B allele in northern India give people more protection against cholera

Question 43

ABO alleles & disease susceptibility

Answer 43

* O allele is more susceptible to the bubonic plague * A allele is more susceptible to small pox * May account for the increased frequency of the B allele in China, India and parts of Russia, which suffered epidemics of both of these diseases * Harvey G. Klein, Scientific American, May 7, 2005

Question 44

O allele and susceptibility to Helicobacter pylori infections

Answer 44

* O allele carriers are more susceptible to Helicobacter pylori infections * Borén et al. Science 1993, 262(5141):1892-1895. Attachment of Helicobacter pylori to human gastric epithelium mediated by blood group antigens.

Question 45

O allele and protection against Plasmodium falciparaum

Answer 45

* It has been suggested that the O allele protects against severe malaria * Fry et al. Hum Mol Genet. 2008 Feb 15;17(4):567-76. Common variation in the ABO glycosyltransferase is associated with susceptibility to severe Plasmodium falciparum malaria.

Question 46

O allele

Answer 46

• Since malaria was not present in the Americas when Homo sapiens migrated in, there would not have been a selective advantage for this allele

Question 47

What was the evolutionary pathway responsible for the high amount of O blood type phenotype in Native Americans?

Answer 47

• Answer: Outcome of demographic history with migration of small population producing a bottleneck which generated in a founder effect which resulted in the high blood O allele frequency in the population which was likely fixed through drift.