blood groups and geography - swisstransfusion groups and geography professeur jacques chiaroni...

Blood Groups and Geography

Professeur Jacques Chiaroni

Anthropologie, Droit, Ethique et Santé

Biology of Blood Groups

RESEARCH FIELD

Biology of Blood Groups 350 Antigens

36 Systems

RESEARCH FIELD


Transfusion Impacts

350 Antigens

36 Systems

RESEARCH FIELD


Transfusion Impacts

Functional Impacts

350 Antigens

36 Systems

RESEARCH FIELD


Transfusion Impacts

Functional Impacts

Geographic

Distribution

350 Antigens

36 Systems

RESEARCH FIELD


Transfusion Impacts

Functional Impacts

Geographic

Distribution

Migrations

No blood donation

Culture

350 Antigens

36 Systems

RESEARCH FIELD

Anthropology of

Blood donation


Transfusion Impacts

Functional Impacts

Geographic

Distribution

WHY ?

Migrations

No blood donation

Culture

350 Antigens

36 Systems

RESEARCH FIELD

Anthropology of

Blood donation


Transfusion Impacts

Functional Impacts

Geographic

Distribution

WHY ?

Migrations

No blood donation

Culture

Other Genetic Markers study

Multidisciplinary approach

Evolutionary Forces Actions :

• Natural and Cultural Selection

• Pre historic migrations

• Genetic Drift

Ancient DNA : AMH & Archaic

350 Antigens

36 Systems

RESEARCH FIELD

Anthropology of

Blood donation

Geographic Distribution of the Blood Groups Antigens

Man – Environment Interactions

1.Infectious Diseases Susceptibility



1.Infectious Diseases Susceptibility

ABO

•Plague : O < A/B

•Smallpox : A/O < B

•Cholera : A/O < B

•Area with Plague + Smallpox + Cholera B↗ (India – China)

•Syphilis : O > A/B

•E.coli O157 – Norovirus : O < A/B

•Helicobacter pylori : O (Leb) < A/B

B



2. However it is the ability to survive malaria which is the most power strength

Epidemiological Studies Overlap of some Hbpathy with current / ancient endemic malaria area Advantage for HTZ




Malaria

Hemoglobinopathies




Concerning Blood groups The attempts to fit by the target (Red Blood Cell) Creating an outer barrier : making the receptors less “receptive” ABO (O) Glycophorines (MNS) Africa : lack of GPB, SEA : lack of GPC (Gerbich -, Melanesia) Bande 3 (Diego) SEA : Less expression (SEAO) CR1 molecules (Knops) Africa : KN*7/KN*7 (Sl(a-)) specific case of Duffy - P.vivax interactions

Malaria

Hemoglobinopathies

Epidemiological Studies Overlap of some Hbpathy with current / ancient endemic malaria area Advantage for HTZ


The history of the settlement also has its say !


The history of the settlement also has its say !

Examples :

• ABO and DIEGO systems and peopling of America

• RH system and the origin and expansion of modern Human

• DUFFY system and Plasmodium vivax

ABO and DIEGO systems and peopling of America

A

B

O

ABO in America

Finding

B has not passed the Bering Strait

A has not passed the Rio Grande

O reached Terra Del Fuego

Why ?

In North Am : A/O only are present

In South Am : 100% of native Americans are O

Hypotheses

Selection

Settlement History (Founder Effect)

Selection ?

A

B

O

Selection ?

Presence of malaria in C and S America

O protects against severe forms

A/O arrived in North Am and went to le South

A/O meet malaria and A didn’t pass the Rio Grande

A

B

O

A/O

O

Malaria area

Selection ?

Presence of malaria in C and S America

O protects against severe forms

A/O arrived in North Am and went to le South

A/O meet malaria and A didn’t pass the Rio Grande

Why O is not exclusive in malaria area ?

O under balanced selection

Positive for some pathologies

Negative for other (susceptibility for HR, UGD…)

A

B

O

A/O

O

Malaria area

Settlement History (Founder Effect) ?


Y Chromosome / mtDNA

Y tree



2 Y-Haplogroupes : C and Q

Signal of Initial Colonization of Central Asia and America

C

Q

Y tree





Diego Blood Group

Dib : in all populations

Dia : in America (some exceptions) / Central Asia (Mongols)

C

Q

Dia

Y tree





Diego Blood Group



Co migration

C with A

C

Q

Dia

A

Y tree





Diego Blood Group



Co migration

C with A

Q / Dia with O

C

Q

Dia

O

A

Y tree





Diego Blood Group



Co migration Peopling > Selection

C with A

Q / Dia with O

C

Q

Dia

O

A

Y tree





Diego Blood Group




C with A

Q / Dia with O

In summary

In North America : O / Q / Dia and A / C

In South America : O / Q / Dia

C

Q

Dia

O

A

Y tree





Diego Blood Group




C with A

Q / Dia with O

In summary

In North America : O / Q / Dia and A / C

In South America : O / Q / Dia

C

Q

Dia

which scenario ?

O

A

Y tree


Paleo climatologic data

• LGM (20/30 KYA), Pacific gate (15KYA), Inland corridor (12,5KYA)

T.Goebel, SCIENCE VOL 319 14 MARCH 2008

Monte Verde

14 675




20/30 000 YEARS : Initial migration from Siberia

• During the LGM

• With ALL the Genetic Markers


Monte Verde

14 675

Q / O / Dia

C / A

Beringian glacial

refugee





• During the LGM


15 000 YEARS : Opening the Pacific gate

1° migration in virgin territory : fast (600 years) and distant (Monte Verde)

Tacking with it : O / Dia / Q


Monte Verde

14 675

Q / O / Dia

Q / O / Dia

Q / O / Dia

C / A

Beringian glacial

refugee





• During the LGM





12 500 YEARS : Opening the Inland corridor

2° migration in occupied territory : restricted to North America

Tacking with it : C / A / without Dia


Monte Verde

14 675

Q / O / Dia

Q / O / Dia

C / A

Q / O / Dia

C / A

Beringian glacial

refugee





• During the LGM








5 000 YEARS (?) : circumpolar migration

3° migration specific C clades / without Dia


Monte Verde

14 675

Q / O / Dia

Q / O / Dia

C / A

Q / O / Dia

C / A

Beringian glacial

refugee





• During the LGM











Monte Verde

14 675

Q / O / Dia

Q / O / Dia

C / A

Q / O / Dia

C / A

Beringian glacial

refugee

3 WAVES





• During the LGM










Linguistic : 3 families of languages

3 WAVES





• During the LGM










All dispersal events • had their source around Beringia • Involved elements of the same gene pool sampled

at different times

Linguistic : 3 families of languages

3 WAVES

Diego secrets

Origin : Central Asia (Mongolia)

Origin : Central Asia (Mongolia) East Expansion : Bering (20KYA) South America (15KYA) Asiatic origin of native america people


• South America : structuration : First farmers (Dia) / Hunter – Gatherer (No Dia) social rules • North America : structuration : Amerind (Dia) / Na-Dene - Eskimo (No Dia)



West Expansion :

• Eurasia : Co migration Dia / Hg C

Origin : Central Asia (Mongolia) East Expansion : Bering (20KYA) South America (15KYA) asiatic origin of native america people


West Expansion :

• Eurasia : Co migration Dia / Hg C expansion signal of • Altaic language, • steppe people since (III) and Mongols (XIII)

RH system and the origin and expansion of modern Human

• D Ce

• D cE

• D ce

• D CE

• d Ce

• d cE

• d ce

• d CE

High Diversity • > 50 Antigens • Lot of variants (alleles) RHD/RHCE

• D Ce

• D cE

• D ce

• D CE

• d Ce

• d cE

• d ce

• d CE

Why R0 is so frequent in Africa ?

High Diversity • > 50 Antigens • Lot of variants (alleles) RHD/RHCE

Why hightest diversity is in Africa ?

Multiregional Out Of Africa

Origin of modern human theories

1.5MA

Multiregional Out Of Africa

Evidences for the Out of Africa model

• Evidences from paleo-anthropology and archeology

• Earliest hominin fossils (4-7 MYA) are found in Africa

• The earliest anatomically modern human fossils are found in Africa 200 KYA

• The oldest tools are found in Africa

• Evidences from the genetic of present day populations : Phylogeny + Diversity level

Origin of modern human theories

1.5MA

Evidence from the genetic of present day populations : PHYLOGENY

Phylogeny

• Recent clades derived from ancient clades


Phylogeny


Results consistent with OOA model

• The deepest clades are in Africa

• Only a part of the most recent phylogeny spread after OOA

• Non African GD is included in African GD


Phylogeny






Blood groups do not escape the rule


Phylogeny








• RHD Phylogeny (Flegel)

Phylogeny








• RHD Phylogeny (Flegel) • Haplotypes Phylogeny (Carrit)

Evidence from the genetic of present day populations : GENETIC DIVERSITY

Genetic Diversity level : Accumulation of diversity requires Time More a population is diverse, More ancient it is High diversity = ancient population The highest genetic diversity is in Africa The diversity decline with the distance from Africa


Genetic Diversity level : Accumulation of diversity requires Time More a population is diverse, More ancient it is The highest genetic diversity is in Africa The diversity decline with the distance from Africa

107 POP 36 000 SAMP



107 POP 36 000 SAMP


This is suggesting • An African origin of AMH and the OOA model • An initial settlement process by serial founder effects • TIMEX consistent with paleo anthropological data


107 POP 36 000 SAMP


Blood groups do not escape the rule • 150 samples (101 Dogons, 46 Fulani) • On 8 RhD negative / 3 molecular backgrounds • 10 different alleles RHD • 11 different alleles RHCE • 35% of people carry a variant vs few % in Europe

This is suggesting • An African origin of AMH and the OOA model • An initial settlement process by serial founder effects • TIMEX consistent with paleo anthropological data

DUFFY system and Plasmodium vivax

FY*A

FY*B

FY*O

FY*A

FY*B

FY*O

• Most prevalent of the 3 alleles in modern human populations • Highest in Asia (90/95%) (reduction of P. vivax infection) • 30-50% in Europe • Present in southern Africa, • Absent in Equatorial Africa

FY*A

FY*B

FY*O


• Ancestral form • DARC in great apes carry FY*B and NO FY*A / *0 • Available archaic hominin genomes (Denisovan, Neanderthal) carry FY*B and NO FY*A /*0 • 50/70% in Europe • Present in southern Africa • Absent in Equatorial Africa

FY*A

FY*B

FY*O



• Mutation in Erythroid Promoter Region of DARC, occurring on a FY*B background • NO protein on erythrocytes • Near fixation in sub-Saharan Africa 99% • Nearly absent in Asia and Europe P. vivax interactions • Geographic overlapping with less P. vivax area • DARC, Receptor for P. vivax • “Total” protection for homozygous individuals, partial for heterozygous individuals

FY*A

FY*B

FY*O



• Mutation in Erythroid Promoter Region of DARC, occurring on a FY*B background • NO protein on erythrocytes • Near fixation in sub-Saharan Africa 99% • Nearly absent in Asia and Europe Hypothesis concerning that fixation : P. vivax interactions • Geographic overlapping with less P. vivax area • DARC, Receptor for P. vivax • “Total” protection for homozygous individuals

FY*0

Classical hypothesis concerning this fixation in equatorial Africa

FY*0 arose in central and west African populations (Bantu and Pygmies)

Under selective pressure, it reaches fixation in equatorial Africa

It expanded to East and South Africa with Bantu expansion (3 000 – 1 500 BC)

When FY*0 fixed, P.vivax disappeared lacking host

Persistence of micro endemic P.vivax in Equatorial East Africa where FY*A is present in Afro-asiatic population (Back to Africa)

Classical hypothesis concerning this fixation in equatorial Africa

FY*0 arose in central and west African populations (Bantu and Pygmies)

Under selective pressure, it reaches fixation in equatorial Africa

It expanded to East and South Africa with Bantu expansion (3 000 – 1 500 BC)

When FY*0 fixed, P.vivax disappeared lacking host

Persistence of micro endemic P.vivax in Equatorial East Africa where FY*A is present in Afro-asiatic population (Back to Africa)

FY*0

Is FY*O fixation in Equatorial Africa due to selection ?


Kimberly F et al, 2016. Sequencing data from • over 1,000 individuals in 21 human populations • ancient human • great ape genomes

YES

FY*0 have reached fixation due to selection With high selection coefficient (0.05) Similar to other loci under strong selection (other malaria resistance alleles) Selection acting over this locus from ancient times FY*0 arose : • Before or during the PYGMIES / BANTU split 50-65KYA • After the initial Out-Of-Africa expansion (70 KYA)


FY*0 have reached fixation due to selection With high selection coefficient (0.05) Similar to other loci under strong selection (other malaria resistance alleles) Selection acting over this locus from ancient times FY*0 arose : • Before or during the PYGMIES / BANTU split 50-65KYA • After the initial Out-Of-Africa expansion (70 KYA)


YES


FY*0 have reached fixation due to selection With high selection coefficient (0.05) Similar to other loci under strong selection (other malaria resistance alleles) Selection acting over this locus from ancient times FY*0 arose : • Around 60 KYA after FY*B (ancestral) and FY*A • Before or during the PYGMIES / BANTU split 50-60KYA • After the initial Out-Of-Africa expansion (70 KYA)


YES

Some problems

Some problems

High selection coefficient not consistent with severity of P. vivax which is currently much lower than that observed for P. falciparum

Some problems


P. vivax was able to evolve to overcome the protective effect of FY*O

Woldearegai et al, 2013. Plasmodium vivax malaria in Duffy-negative individuals from Ethiopia.

Ryan JR et al, 2006. Evidence for transmission of Plasmodium vivax among a duffy antigen negative population in Western Kenya.

Menard D et al, 2010. Plasmodium vivax clinical malaria is commonly observed in Duffy-negative Malagasy people.

Wurtz N et al, 2011. Vivax malaria in Mauritania includes infection of a Duffy-negative individual.

Cavasini CE et al, 2007. Plasmodium vivax infection among Duffy antigen-negative individuals from the Brazilian Amazon region: an exception?

Pasvol G, 2007. Eroding the resistance of Duffy negativity to invasion by Plasmodium vivax? In Brazil

Some problems


P. vivax was able to evolve to overcome the protective effect of FY*O

Relative quick adaptation

Since the first contact between African slaves carrying FY*0 and South American P.vivax endemy

Woldearegai et al, 2013. Plasmodium vivax malaria in Duffy-negative individuals from Ethiopia.

Ryan JR et al, 2006. Evidence for transmission of Plasmodium vivax among a duffy antigen negative population in Western Kenya.

Menard D et al, 2010. Plasmodium vivax clinical malaria is commonly observed in Duffy-negative Malagasy people.

Wurtz N et al, 2011. Vivax malaria in Mauritania includes infection of a Duffy-negative individual.

Cavasini CE et al, 2007. Plasmodium vivax infection among Duffy antigen-negative individuals from the Brazilian Amazon region: an exception?

Pasvol G, 2007. Eroding the resistance of Duffy negativity to invasion by Plasmodium vivax? In Brazil

Some remaining questions


Considering that P.vivax is the factor of selection in Africa

Considering that the contact FY*0 and P.vivax could date back to 60 KYA (T MRCA FY*0)

Considering that P.vivax was able to adapt VERY RAPIDLY in South America

Considering that P.vivax is the factor of selection in Africa

Considering that the contact FY*0 and P.vivax could date back to 60 KYA (T MRCA FY*0)

Considering that P.vivax was able to adapt VERY RAPIDLY in South America

Why did he not adapted Africa ?

Was P.vivax the selective pressure for the FY*O in Equatorial Africa ?


P. vivax disappeared or never been in Africa ?

MEDICAL CONSEQUENCES OF THESE MIGRATIONS Example : Blood Transfusion Impacts of biological and cultural diversity of population on : Transfusion practices for recipients : Complex cases exploration in IH, Molecular Biology use Reagents selected by geographic origin of recipients (panels, antibodies, primers) Transfusion practices for donors : anthropological approach for blood donation in minorities detection of variants according the geographic origin of the donors rare donors panels

blood groups and geography - swisstransfusion groups and geography professeur jacques chiaroni...

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