American University of Armenia Biological Anthropology Questions

1. What is the HLA complex? Why is it so variable in our species?

2. Discuss the terms ‘biocultural evolution’, ‘balanced polymorphism’, heterozygote advantage’ using sickle cell anemia as an example?

3. What is the Bombay Blood type- and what is its relationship to the ABO system?

4. Using the ABO blood system as an example- discuss the terms antigen and antibody.

Blood Groups and Proteins 1
Definitions
• Antibodies (Immunoglobulins) – protein
molecules that attach to foreign substances
rendering them harmless
• Antigens – foreign substances that stimulate
the synthesis of antibodies
• Agglutination – attachment of antibodies +
antigens
ABO(H) Blood Group
• ABO Locus on chromosome #9
• Antibodies present without previous exposure
• At least 7 exons long
• Single nucleotide deletion in exon 6 = O Blood
• 7 substitutions in Exons 6 and 7 determine
differences between A and B
• Actually 4 Alleles – A1, A2 (1/4 antigens), B, O(H)
ABO Blood Group
H Antigen
• Found on virtually all RBCs
• Chromosome #19 – One antigen (H and h alleles)
• Building block for the ABO system
• Deficiency = Bombay blood type (hh) –
transfusion from normal “O” causes severe
reaction
• If no H – then cannot have A or B
• 1 of 8,000 in Taiwan, 1 of 10,000 in India, and 1
per million in Europe
ABH Blood Group
Paternity Determination Complications
with Bombay
Child is Ohh – Therefore Alan is Father
ABO Blood Groups
• Three alleles not evenly distributed around
world
• O allele is the most common throughout the
world, followed by A, B is rarest.
• Interesting patterns in Americas, Australia and
Europe.
A Allele Distribution
B Allele Distribution
ABO and Diseases
• Cholera – O = increased risk of infection and
stronger symptoms
• Syphilis – O blood = more resistant
• Plague (Anti O) –presence of H antigen
protects
• Smallpox – Anti A (O and B do better).
• Mosquitoes prefer O
• Infantile diarrhea – worse in A and B
Differential Fertility
• O women < fertility with A or B men • OO women x AO or BO man > expected # of
OO children
– prezygotic – Vaginal antibodies react with A or B
sperm)
– Postzygotic – increased spontaneous abortion
when maternal and fetal blood types are
incompatible
– Should lead to eventual fixation of O
Rhesus Factor
• Three loci (CcDdEe) on (Chromosome #1)
• Dd most important (D = +, d = -)
• Antibodies NOT present without exposure
• Hemolytic disease of newborn
• Generally Rh- high in Europeans (40%)
• Africans Rh- (25 %)
• Native Americans and Native Australians
almost 100% Rh+
MNS System
• Chromosome #4
• Two codominant alleles (MN) (GPA gene)
• Closely linked S (Ss) (GPB gene)
• Passed on as haplotye (MS, Ms, NS, Ns)
• High levels of MS and Ms in Native Americans
• High frequencies of N in Native Australians and
New Guineans
• Total lack of S among Native Australians, but high
amongst Native New Guineans
• Potential link to Malaria and influenza
Duffy System
• Chromosome #1
• Three alleles – Fya Fyb, Fyo
• Phenotypes Fy(a+ b+), Fy(a-b+), Fy(a+b-), Fy(ab-)
• Fy(a-b-) = 100% Africans – may be
hypersensitive to blood transfusion of duffy +
blood (a or b)
• Fy (a-b-) protected from malaria disease (not
infection)
Hemoglobin Variants
Hemoglobin
• Large complex molecule
• Four long amino acid
chains
• Each chain
encompasses heme
group = which binds to
oxygen transporting it
around body and
releasing as needed
Sickle Cell Anemia
• Single point mutation altered and less
efficient form of
hemoglobin
• Potentially lethal
especially during
strenuous exercise (life
expectancy = 40 years
in USA, lower in Africa)
• 100,000 deaths per year
world wide
Genetics
• Two alleles – HbA (normal), HbS (sickle) –
Incomplete dominance
• HbA, HbA = normal RBCs
• HbS, HbS = Sickle cell disease
• HbA, HbS = carrier (variable effects)
• Two carriers have 25% chance of having child
with SCD = 1/400 births in African Americans
Sickle Cell Anemia
Physiological effects
Sickle Cell/Malaria Association
• Heterozygote advantage – cells less able to
support malarial parasite growth, longer life
span, higher fertility
• Balanced Polymorphism
• Biocultural Evolution
Malaria
• Lethal, mosquito-borne
• Plasmodium spp. (4 species in humans P.
vivax, P. ovale, P. malariae, and P. falciparum)
• Anopheles mosquitos
• Endemic to most tropical areas
• Approx. 2 million deaths worldwide annually
Malaria Life Cycle
Sickle Cell Video
Type E Hemoglobin
• Mutation in the β globin gene
• Third most common Hb variant
(HbA>HbS>HbE)
• Highest frequencies in South and Southeast
Asia (Hb E approaches 60% in many regions of
Thailand, Laos and Cambodia)
• HbE, HbE ≠ severe anemia
• HbA, HbE – resistant to malaria
Thalassemia
• Complete synthesis of either α or β chain
disrupted
• Frame shifts mutations – entire sequence
changes, chain shorter or absent entirely
• Severe anemia, 100,000 childhood deaths per
year
Thalassemia major
• β Thalassema
• Autosomal dominant on chromosome #11
• Decreases or halts synthesis of beta-Hb chain
• Unstable RBCs (lethal in homozygotes)
• Multiple mutation sites (some more lethal
than others), vary by region
Alpha Thalassemia
• Deficiency of alpha-Hb chain
• Two loci on chromosome #16
• Mild-lethal symptoms
• Frequencies follow distribution of malaria
• New Guinea =- 22-68% on coast (malaria
present) versus 2-5% in highlands (malaria not
present)
Sardinia
• 1.5 million people
• Isolated villages
• Genetic markers vary by
area
• Malaria major problem
in some areas prior to
1944
Decline of Thalassemia
Sardinia
• Inverse relationship of
G6PD and Thalassemia
with altitude
• Villages not fitting
pattern – recent
immigrants
Genetics of African Americans
• Reduction in frequency of HbS (5% versus 15%
in Africa).
• Reduction of malarial pressure – and genetic
admixture
• Areas with lowest rates of admixture and
highest historical rates of malaria show
highest HbS rates today
Gullah Islands
• Coastal South Carolina
• Most recent persistence
of malaria
• Cultural isolation
• Highest rates of HbS
and (16%)
• Video
Beta Globin RFLPS
African Hb Haplotypes in the New World
HAPLOTY JAMAICA UNITED
PE
STATES
BRAZIL
SENEGAL 10
15
1
BENIN
72
62
26
BANTU
(CAR)
17
18
73
Origins of Slaves Taken From Africa
Variability in HB Haplotypes
• Haplotypes vary in
severity of HbS.
• Senegal – retention of
more HbF – prevents
cell distortion
• Benin – less HbF – SCD
more severe.
ANTH 311 Fall 2022: Test #2 Review Sheet
Blood Proteins
Antibodies, antigens, agglutination
ABO blood groups
H – antigen – Bombay blood type
Distribution of different Alleles
Differential fertility of women with O blood
ABO and diseases
Rhesus factor – genetics, problems with childbirth, distribution
MNS system
Duffy system
Serum Proteins
IgG Immunoglobulins
Haptoglobins – Hp1, Hp2
Transferrins – TfC, TfD, TfB
Lipoproteins – APO A, APO C and APO E
G6PD Deficiency/Favism
Sex-linked (X) males vs females, genotypes, GdA-, Gdmed – distribution
Favism and Malaria
Why G6PD so prevalent?
HLA Definitions
HLA – Human Leukocyte Antigens (MHC), immunity
HLA Genes
Variation in HLA Haplotypes – hypervariable
Linkage Disequlibrium
HLA and Disease
Link between HLA and Disease
Ankylosing Spondilitis
Mate Choice
Hemoglobin Variants
Structure and function of hemoglobin
Sickle Cell Anemia – genetics, distribution, association with malaria, balanced polymorphism,
biocultural evolution (slash and burn agriculture)
Type E hemoglobin – genetics, distribution, relationship to malaria
Thalassemia – major and alpha, genetics, distribution, relationship to malaria
Malaria – life cycle
Sardinia – malaria and Thalassemia
African Americans and Sickle Cell, Gullah Islands
Hemoglobin haplotypes and slave trade
Lactose, Ear Wax and Taste
Lactose Tolerance – genetics, distribution, biocultural evolution
Cerumen, two types – genetics, distribution, relationship to body odor, relationship to breast
cancer
PTC tasting – threshold levels, genetics, amino acid polymorphisms, distribution, evolutionary
significance
Asparagus and urine odor – genetics
Cilantro and soap taste – distribution