HLA in Jaidukama: an Amerindian secluded Colombianpopulation with new haplotypes and Asian and Pacific-sharedalleles

J. Martinez-Laso • F. Montoya • C. Areces • J. Moscoso •

C. Silvera • D. Rey • C. Parga-Lozano • P. Gomez-Prieto •

M. Enriquez de Salamanca • A. Arnaiz-Villena

Received: 24 September 2010 / Accepted: 9 November 2010 / Published online: 26 November 2010

� Springer Science+Business Media B.V. 2010

Abstract America first inhabitants and peopling are still

debated. In order to increase knowledge about these

questions, we have aimed to detect HLA genes of an

Amerindian secluded community: Jaidukama, who lives in

North Colombia Equatorial forest. HLA genotyping and

extended haplotype calculations were carried out in 39

healthy individuals belonging to 13 families. HLA fre-

quencies were compared to other Amerindians and

worldwide populations by calculating genetic distances,

relatedness dendrograms and correspondence analyses.

Only four DRB1 alleles were found (*0404, *0407, *1402

and *1602); however a total of 17 Amerindian different

extended class I–class II HLA haplotypes were directly

counted from the family studies, nine of them were specific

of Jaidukamas. Some of the alleles or group of alleles

within an extended haplotype (i.e. DQB1–DRB1) were also

found in Asians and Pacific Islanders, further supporting

existence of Asian and Pacific gene flow with Amerindians

or a common founder effect. It is further supported that

HLA extended haplotypes vary faster than alleles in pop-

ulations. It is concluded that this unique model of Amer-

indian secluded families study suggests that rapid HLA

haplotype variation may be more important than allele

variation for survival (starting immune responses). This

work may also be useful for future transplant programs in

the area.

Keywords Jaidukama � Colombia � Amerindians � HLA �America peopling

Introduction

The first Amerindian natives are postulated to have come

from Asia through the Bering land bridge between 30,000

and 12,000 years before the present (BP). These conclu-

sions have been based on cultural, morphological and

genetic similarities between American and Asian popula-

tions. Both Siberia [1] and Mongolia [2, 3] have been put

forward as the most likely places of origin in Asia.

Greenberg first postulated the triple migration theory for

explaining the peopling of the Americas [4]: Amerindians

(most North and South American Indians; 12,000 years

BP), Na-Dene (Athabascans, Navajo, Apache; 8,000 years

BP) and Eskimo-Aleuts (6,000 years BP) [5]. Some studies

have or have not supported the hypothesis by Y Chr and

mtDNA markers [2, 3, 6–12]. However these conclusions

do not explain all linguistic and genetic findings [13–15].

Y Chr and mtDNA studies seem unable to definitively

clarify American people and Amerindian origins, mainly

The authors J. Martinez-Laso and F. Montoya contributed equally for

this work and the order of authorship is arbitrary.

J. Martinez-Laso

Unidad de Inmunoterapia Celular, Centro Nacional de

Microbiologıa, Instituto de Salud Carlos III, Madrid, Spain

F. Montoya

Section of Immunology, Corporacion para Investigaciones

Biologicas, Medellin, Colombia

C. Areces � J. Moscoso � C. Silvera � D. Rey �C. Parga-Lozano � P. Gomez-Prieto �M. Enriquez de Salamanca � A. Arnaiz-Villena

Department of Immunology, University Complutense,

The Madrid Regional Blood Center, Madrid, Spain

A. Arnaiz-Villena (&)

Departamento de Inmunologia, Facultad de Medicina,

Universidad Complutense, Pabellon 5, planta 4. Avda.

Complutense s/n, Madrid 28040, Spain

e-mail: aarnaiz@med.ucm.es

URL: http://chopo.pntic.mec.es/biolmol/

123

Mol Biol Rep (2011) 38:3689–3701

DOI 10.1007/s11033-010-0483-6

because the studies have been gene—rather than popula-

tion—based. Their emphasis has been on variant genealo-

gies rather than on population frequencies studies. In this

regard HLA data may be more informative [16] because

maternal and paternal lineages and both frequencies (i.e.:

genetic distances, dendrograms and correspondence anal-

yses) and genealogies (quasi-specific HLA alleles and

haplotypes) may be studied for comparing populations.

Recently, new mtDNA analysis has suggested that all

mtDNA lineages must have been isolated in Asia before

entering the New World by at least 7,000–15,000 years.

They even suggest that this place must have been Beringia

[17]. Also, a dispersal of Amerindians coming from Asia

has been put forward through Coastal Pacific line [18]

based on all available archaeological, anthropological and

mtDNA and other genetic data. A Trans-Pacific route of

American peopling from Asia or Polynesia had been sug-

gested because HTLV-1 virus strains shared identical

sequences in Japan and in the northern coast of South

America [19] and some HLA alleles may have been

introduced by the same Trans-Pacific route [20]. Finally,

both genetic [21] and archaeological [22] evidence sug-

gests that a two-way Trans-Atlantic traffic occurred before

Columbus discovered America. Archaeologists in New

Mexico have also found tools used 20,000 years ago in

Spanish Solutrean culture [22]. Recently our own studies

by using autosomic HLA markers and combining geneal-

ogies particular markers and population gene frequencies

comparisons, show that Asian, Polinesian and Oceania

gene flow with Amerindians has been possible [15].

On the other hand, the first Colombian settlers arrived

about 40,000 years ago. El Abra site is one of the most

ancient and completely studied of human occupation

finding. (http://todacolombia.com/etapasprecolobinas.html)

(Fig. 1). Embera speaking Amerindians are postulated to

have come to Jaidukama ethnic group placement through

Panama or through Caribbean Islands Arch, following

the Orinocco River basin (http://todacolombia.com/

etapasprecolobinas.html; (Fig. 1). However the amount of

Panama Embera speakers makes it difficult the arrival

through other ways different to Panama. Jaidukama ethnic

group placement is presently close to Ituango city (Antio-

quia, Colombia). Only in the last years have been

Fig. 1 Jaidukama ethnic group placement is presently close to

Ituango city, Antioquia province, Colombia. Yellow colour: Areas

where Embera Katıo language is used. (Color figure online)

Fig. 2 Jaidukama’s dwellings are built on stakes and are separated by

extensive areas of forest vegetation. They form small concentration of

round type houses, usually inhabited by related people

3690 Mol Biol Rep (2011) 38:3689–3701

123

Jaidukama visited regularly and recently by urbanized I-

tuango city inhabitants. Jaidukama speak Embera-Katio

dialect (http://www.ituango-antioquia.gov.co/index.shtml).

This very much secluded Jaidumaka Amerindian popula-

tion belongs to the ethnic and linguistic Embera group,

which is spoken by some 30,000 Amerindians and exhibit a

scattered settlement pattern in Panama and Colombia

(todacolombia.com/etapasprecolobinas.html).

In the present work, we have studied the HLA gene

profile in the Embera-Katio speaking community of the

Jaidukama Amerindians and compared it with other North

and South American First Inhabitants and worldwide

populations. Our aims are: (1) To determine the HLA class

I (-A and -B) and class II (-DRB1, -DQA1 and -DQB1)

Jaidukama alleles by using indirect DNA sequencing, (2) to

establish real haplotypes by family studies and (3) to

compare the Jaidukama HLA profile with that of other First

American Natives and other worldwide populations in

order to clarify the much debated peopling of the Americas

and in order to establish future transplant and epidemiology

programs of HLA marker diseases.

Materials and methods

Thirty-nine healthy individuals belonging to 13 families

including the father, mother and one child were HLA class

I and class II typed. Whenever a parent was missing,

Table 1 Populations studied in the present work. A total of 12,202 chromosomes were analyzed and geographical locations are represented in

Fig. 1

Identification

number

Population n Reference Identification

number

Population N Reference

1 Mazatecan 89 Arnaiz-Villena et al. [32] 24 Koryaks 92 Grahovac et al. [60]

2 Seri 100 Petzl-Erler et al. [56] 25 Chukchi 59 Grahovac et al. [60]

3 Mixe 55 Petzl-Erler et al. [56] 26 Kets 22 Grahovac et al. [60]

4 Mixteco 103 Petzl-Erler et al. [56] 27 Evenks 35 Grahovac et al. [60]

5 Zapoteco 75 Petzl-Erler et al. [56] 28 Singapore-Chinese 71 Imanishi et al. [33, 34]

6 Mexican Mestizo 99 Vargas-Alarcon et al. [80] 29 Buyi 70 Imanishi et al. [33, 34]

7 Wayuu 112 Yunis et al. [54] 30 Manchu 50 Geng et al. [69]

8 Arhuaco 123 Yunis et al. [54] 31 Korean 100 Imanishi et al. [33, 34]

9 Kogi 67 Yunis et al. [54] 32 Japanese 493 Imanishi et al. [33, 34]

10 Arsario 20 Yunis et al. [54] 33 Khalk-Mongolian 202 Munkhbat et al. [59]

11 Cayapa 100 Titus-Trachtenberg et al. [55] 34 Tuvins 197 Martinez-Laso et al. [70]

12 Xavantes 74 Cerna et al. [20] 35 Khoton-Mongolian 85 Munkhbat et al. [59]

13 Guarani 32 Cerna et al. [20] 36 Germans 295 Imanishi et al. [33, 34]

14 Toba-Pilaga 19 Cerna et al. [20] 37 Sardinians 91 Imanishi et al. [33, 34]

15 Mataco- Wichi 49 Cerna et al. [20] 38 Italians 284 Imanishi et al. [33, 34]

16 Eastern-Toba 135 Cerna et al. [20] 39 French 179 Imanishi et al. [33, 34]

17 Jaidukama 39 Present study 40 Spaniards 176 Martinez-Laso et al. [27]

18 Aymara 101 Arnaiz-Villena et al. [66] 41 Spanish-Basques 80 Martinez-Laso et al. [27]

19 Eskimos 35 Grahovac et al. [60] 42 Algerians 102 Arnaiz-Villena et al. [71]

20 Athabascan 124 Monsalve et al. [58] 43 Berbers 98 Izaabel et al. [72]

21 Tlingit 53 Imanishi et al. [33, 34] 44 Morocans 98 Gomez-Casado et al. [73]

22 Nivkhs 32 Grahovac et al. [60] 45 West Samoa 102 Gao et al. [75]

23 Udegeys 23 Grahovac et al. [60] 46 Madang 65 Gao et al. [74, 75, 76]

47 Rabaul 60 Gao et al. [74, 75, 76] 54 Cape York 80 Gao et al. [74, 75, 76]

48 New Caledonia . 65 Gao et al. [74, 75, 76] 55 South African Blacks 59 Imanishi et al. [33, 34]

49 Fiji 57 Gao et al. [74, 75, 76] 56 North American

Blacks

447 Imanishi et al. [33, 34]

50 Papua New Guinean 57 Gao et al. [74, 75, 76] 57 Hottentot 65 Imanishi et al. [33, 34]

51 Central Desert 152 Lester et al. [77] 58 Bushmen 103 Imanishi et al. [33, 34]

52 Yuendumu 119 Lester et al. [77] 59 Ainu 50 Bannai et al. [61]

53 Kimberley 82 Gao et al. [74, 75, 76]

West Samoa From Central Polynesia, Madang Melanesians on the North New Guinea mainland Coast, Rabaul Melanesians in New Britain, NewCaledonia Melanesians from Noumea, Fiji From largest Fijian island; Central desert, Yuendumu, Kimberley, and Cape York: Australian aborigines

Mol Biol Rep (2011) 38:3689–3701 3691

123

samples were taken from two of the children in order to

construct the full parental HLA haplotypes.

The samples were extracted and rapidly transported by

helicopter to the CIB (Corporacion para Investigaciones

Biologicas) laboratories in Medellin. The Jaidukama set-

tlement is located in the northwestern part of the Antioquia

province (Fig. 1). There were 157 Jaidukama Amerindians

distributed among 27 families that inhabit 27 tambos (areas

separated from other families); these natives were in this

place probably since long time ago surrounded by a thick

forest. Blood from volunteers were taken in the frameshift

of a preventive and epidemiology work. Full consent was

given by Jaidukama volunteers. Their dwellings are char-

acteristically built on stakes and are separated by extensive

areas of forest vegetation that require several hours of walk

between dwellings. They form small concentrations of

three to four round-type houses according to parental ties

(Fig. 2). The main source of nourishment is constituted by

plantains, corn and beans. Women know only the local

dialect (a specific Embera-Katio one) and men are in

charge of communication between neighboring ethnic

groups, which leads to think there has not been much

mixing with other races since they establishment in site.

Each individual studied was born in the Antioquia forest or

other small urban areas, had a Jaidukama physical aspect

and their parents had been born in this area; they also spoke

the specific Embera-Katio dialect [23, 24]. The origin of all

other populations used for comparisons are detailed in

Table 1; a total of 12,202 chromosomes were studied. It

includes populations from different origins, Caucasoids,

Orientals, Negroids, Polynesians, Micronesians, Na-Dene,

Eskimos and Amerindians. Particularly, the Amerindians

includes groups from, Macro-Mixteco (Mixtecan and

Zapotecan), Macro-Maya (Mixe), Macro-Yuma (Seris),

Chibcha (Arsario, Kogi, Arhuaco and Cayapa), Arawak

(Wayu) and Ge Pano Caribe (Xavantes, Mataco and Toba)

linguistic families [23, 24] (Fig. 5).

HLA genotyping and DNA sequencing

Generic HLA class I (A and B) genotyping was done by a

PCR-SSO technique as previously described [25] with

slight modifications that yield a resolution equivalent to the

standard serology techniques (see Results and Discussion

and Table 2). Reverse dot-blot technique with the Auto-

mated Innolipa system (Innogenetics N.V., Zwijndrecht,

Belgium) were used when oligotyping yield ambiguous

results. High Resolution HLA class II (DRB1 DQA1, and

DQB1) was performed by using reverse dot-blot technique

with the Automated Innolipa system (Innogenetics N.V.,

Zwijndrecht, Belgium). HLA-A, -B, -DRB1, -DQA1, and -

DQB1 allele DNA sequencing was only done when indirect

DNA typing yielded ambiguous results as described in

detail by [26]. High resolution HLA-B typing was made by

sequencing technology as previously described [27–29].

Statistical analysis

Statistical analysis was performed with Arlequin vl.l soft-

ware kindly provided by [30]. In summary, this program

calculated HLA-A, -B, -DRB1, -DQA1 and -DQB1 allele

frequencies, Hardy–Weinberg equilibrium and the linkage

disequilibrium between two alleles at two different loci.

Their level of significance (P) for 2 9 2 comparisons was

determined as previously described [31]. In addition, the

most frequent complete haplotypes were tentatively

deduced from: (1) the 2, 3, and 4 HLA loci haplotype

frequencies [32]; (2) the previously described haplotypes in

other populations [33]; and (3) haplotypes if they appeared

in two or more individuals and the alternative haplotype

was well defined [33]. In order to compare phenotype and

haplotype HLA frequencies with other populations, the

reference tables of the 11th and 12th International HLA

Workshops were used [34, 35] (also see Table 1). Phylo-

genetic trees (dendrograms) were constructed with the

allelic frequencies by using the Neighbor-Joining (NJ)

method [36] with the genetic distances between popula-

tions [37], by using the software DISPAN which contain

the programs GNKDST and TREEVIEW [38, 39]. Corre-

spondence analysis in three dimensions and its bidimen-

sional representation was carried out by using the VISTA

v5.02 computer program [40] (http://forrest.psych.unc.edu).

Table 2 Allele frequencies in Jaidukama Amerindians (Only unre-

lated parents are considered)

Alleles Allele frequencies (%)

HLA-A

A*02 30.8

A*24 69.2

HLA-B

B*35 50.0

B*39 9.6

B*40 7.7

B*51 32.7

HLA-DRB1*

1602 23.1

0407 32.7

1402 28.8

0404 15.4

HLA-DQB1*

301 44.2

302 55.8

DRB1*0404, 0407, 1402 and 1604 are Amerindian alleles which are

also found in other American, Asian or Pacific populations [47]

3692 Mol Biol Rep (2011) 38:3689–3701

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Table 3 HLA haplotypes distribution in Jaidukama Amerindian families (segregation analysis)

Extended HLA haplotypes

HLA-A HLA-B HLA-DRB1 HLA-DQA1 HLA-DQB1

Family 1

F A24 B40 DRB1*1602 DQA1*0501 DQB1*0301

A24 B35 DRB1*1402 DQA1*0501 DQB1*0301

M A24 B35(*3510) DRB1*1602 DQA1*0501 DQB1*0301

A24 B35(*3501) DRB1*1402 DQA1*0501 DQB1*0301

S A24 B35 DRB1*1602 DQA1*0501 DQB1*0301

A24 B35 DRB1*1402 DQA1*0501 DQB1*0301

Family 2

F A24 B39 DRB1*1402 DQA1*0501 DQB1*0301

A2 B40 DRB1*0407 DQA1*03 DQB1*0302

M A2 B40 DRB1*1402 DQA1*0501 DQB1*0301

A24 B35 DRB1*1402 DQA1*0501 DQB1*0301

S A2 B40 DRB1*0407 DQA1*03 DQB1*0302

A24 B35 DRB1*1402 DQA1*0501 DQB1*0301

Family 3

F A2 B35 DRB1*0404 DQA1*03 DQB1*0302

A24 B40 DRB1*0407 DQA1*03 DQB1*0302

M A24 B35(*3501) DRB1*0407 DQA1*03 DQB1*0302

A2 B51 DRB1*0407 DQA1*03 DQB1*0302

S A2 B35 DRB1*0404 DQA1*03 DQB1*0302

A2 B51 DRB1*0407 DQA1*03 DQB1*0302

Family 4

F A24 B35(*3510) DRB1*1602 DQA1*0501 DQB1*0301

A24 B40 DRB1*1402 DQA1*0501 DQB1*0301

M A24 B35 DRB1*1402 DQA1*0501 DQB1*0301

A24 B40 DRB1*1602 DQA1*0501 DQB1*0301

S A24 B40 DRB1*1602 DQA1*0501 DQB1*0301

A24 B40 DRB1*1402 DQA1*0501 DQB1*0301

Family 5

F A2 B40 DRB1*1402 DQA1*0501 DQB1*0301

A24 B35(*3504) DRB1*0404 DQA1*03 DQB1*0302

M A2 B40 DRB1*1402 DQA1*0501 DQB1*0301

A24 B35(*3510) DRB1*1602 DQA1*0501 DQB1*0301

S A24 B35 DRB1*1602 DQA1*0501 DQB1*0301

A24 B35 DRB1*0404 DQA1*03 DQB1*0302

Family 6

F A2 B51 DRB1*0404 DQA1*03 DQB1*0302

A2 B40 DRB1*0404 DQA1*03 DQB1*0302

M A24 B35(*3501) DRB1*0407 DQA1*03 DQB1*0302

A24 B35 DRB1*1402 DQA1*0501 DQB1*0301

S A2 B51 DRB1*0404 DQA1*03 DQB1*0302

A24 B35 DRB1*1402 DQA1*0501 DQB1*0301

Family 7

F A24 B35(*3504) DRB1*0404 DQA1*03 DQB1*0302

A2 B35 DRB1*0407 DQA1*03 DQB1*0302

M A24 B40 DRB1*1402 DQA1*0501 DQB1*0301

A2 B35 DRB1*0407 DQA1*03 DQB1*0302

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Table 3 continued

Extended HLA haplotypes

HLA-A HLA-B HLA-DRB1 HLA-DQA1 HLA-DQB1

S A2 B35 DRB1*0407 DQA1*03 DQB1*0302

A2 B35 DRB1*0407 DQA1*03 DQB1*0302

Family 8

F A24 B40 DRB1*0407 DQA1*03 DQB1*0302

A2 B35 DRB1*0407 DQA1*03 DQB1*0302

M A2 B35 DRB1*0407 DQA1*03 DQB1*0302

A24 B39 DRB1*0407 DQA1*03 DQB1*0302

S A2 B35 DRB1*0407 DQA1*03 DQB1*0302

A24 B40 DRB1*0407 DQA1*03 DQB1*0302

Family 9

F A2 B51 DRB1*0404 DQA1*03 DQB1*0302

A24 B35(*3504) DRB1*0404 DQA1*03 DQB1*0302

M A2 B40 DRB1*0404 DQA1*03 DQB1*0302

A24 B39(*3905) DRB1*1402 DQA1*050 DQB1*0301

S A24 B35(*3504) DRB1*0404 DQA1*03 DQB1*0302

A24 B39(*3905) DRB1*1402 DQA1*050 DQB1*0301

Family 10

F A24 B35(*3501) DRB1*0407 DQA1*03 DQB1*0302

A24 B35(*3504) DRB1*0404 DQA1*03 DQB1*0302

M A24 B35(*3510) DRB1*1602 DQA1*050 DQB1*0301

A24 B40 DRB1*1402 DQA1*050 DQB1*0301

S A24 B35 DRB1*0407 DQA1*03 DQB1*0302

A24 B40 DRB1*1402 DQA1*050 DQB1*0301

Family 11

F A24 B35(*3501) DRB1*0407 DQA1*03 DQB1*0302

A24 B35(*3504) DRB1*0404 DQA1*03 DQB1*0302

M A24 B40 DRB1*1402 DQA1*050 DQB1*0301

A2 B35 DRB1*0407 DQA1*03 DQB1*0302

S A24 B35 DRB1*0407 DQA1*03 DQB1*0302

A2 B35 DRB1*0407 DQA1*03 DQB1*0302

Family 12

F A2 B51 DRB1*0404 DQA1*03 DQB1*0302

A24 B40 DRB1*1402 DQA1*050 DQB1*0301

M A24 B35(*3510) DRB1*1602 DQA1*050 DQB1*0301

A24 B39(*3905) DRB1*1402 DQA1*050 DQB1*0301

S A24 B39 DRB1*1402 DQA1*050 DQB1*0301

A24 B40 DRB1*1402 DQA1*050 DQB1*0301

Family 13

F A24 B35(*3501) DRB1*0407 DQA1*03 DQB1*0302

A24 B39 DRB1*0407 DQA1*03 DQB1*0302

M A24 B40 DRB1*1602 DQA1*050 DQB1*0301

A24 B40 DRB1*0404 DQA1*03 DQB1*0302

S1 A24 B35(*3501) DRB1*0407 DQA1*03 DQB1*0302

A24 B40 DRB1*1602 DQA1*050 DQB1*0301

S2 A24 B40 DRB1*0404 DQA1*03 DQB1*0302

A24 B35 DRB1*0407 DQA1*03 DQB1*0302

* Deduced from HLA siblings typings

3694 Mol Biol Rep (2011) 38:3689–3701

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Correspondence analysis consists of a geometric technique

that may be used for displaying a global view of the rela-

tionships among populations according to HLA (or other)

allele frequencies. This methodology is based on the allelic

frequency variance among populations (similarly to the

classical components methodology) and on the display of

statistical visualization of the differences.

Results and discussion

Characteristic HLA allele frequencies of the Jaidukama

Amerindian population compared to other populations

Table 2 shows the HLA allele frequencies found in the

Jaidukama population. Two different HLA-A (A2 and A24)

and four different HLA-B (B35, B39, B40 and B51) genetic

alleles were found in the Jaidukama ethnic group. HLA-B

subtypes were determined in a few number of individuals by

DNA sequencing due to the lack of sufficient DNA amount.

Alleles found were B*3501, B*3504, B*3510, B*3905,

B*4002 and B*4004 (see Table 3). These alleles have been

previously described in Amerindians [27, 28, 41–43] and

now are included in some extended haplotypes. Regarding

to the HLA class II alleles, four different DRB1 alleles were

found at similar frequencies (DRB 1*0404, *0407, *1602

and *1402) in the studied population, DRB 1*0404 allele

has been also found in Eastern Island [44–46]; all four

DRB1 alleles have been found in well defined Asian and/or

Pacific ethnic groups [47]. DQB1 allele frequencies reflect

the DRB1 locus allele distribution due to the strong linkage

disequilibrium between these two loci and confirmed by

family studies (see Table 3). Data reported in this study on

HLA class I and class II polymorphism are concordant with

those previously described in other ethnic Amerindian

groups [20, 48–53]. It is striking that B35 family has several

variants in such small relatively reduced group. If this is so,

it would mean that relative inbreeding might enhance gene

conversion events, and diversification.

Two types of analyses were done in order to compare

Jaidukama HLA frequencies with other world population

frequencies using unrelated parents (n = 26): (1) with

pooled DRB1 and DQB1 data; and (2) with DRB1 only. It

was impossible to do a study comparing HLA class I allele

frequencies or HLA class I and II conjointly due to the lack

of class I studies (particularly in high resolution) in many

Amerindians and other populations. The DRB1 study was

made to compare the Amerindian HLA population fre-

quencies with those of Polynesians, Melanesians and

Micronesians who lacked DQB1 analyses (Table l).

Fig. 3 Neighbor-Joining (NJ) dendrogram shows relationships

between Jaidukama and other Amerindians, Caucasoids, Na-Dene/

Eskimos and Orientals. Genetic distances between populations were

calculated from HLA-DRB1 and -DQB1 frequencies. Populations

used for study are: Mazatecos [57]; Seri [56]; Mixe [56]; Mixteco

[56]; Zapoteco [56]; Mexican Mestizo (Unpublished); Arhuaco [54];

Kogi [54]; Arsario [54]; Cayapa [55]; Xavante [20]; Guarani [56];

Toba-Pilaga [20]; Mataco-Wichi [20]; Eastern-Toba [20]; Jaidukama

(Present study); Eskimos [60]; Athabascans [58]; Tlingit [33]; Nivkhs

[60]; Udegeys [60]; Koryaks [60]; Chukchi [60]; Kets [60]; Evenks

[33]; Singapore-Chinese [33]; Buyi [33]; Manchu [69]; Coreans [33];

Japonese [33]; Khalk-Mongolians [59]; Tuvins [70]; Khoton-Mon-

golians [59]; Germans [33]; Sardinians [33]; Italians [33]; French

[33]; Spanish [32]; Spanish-Basque [32]; Algerians [71]; Moroccan-

Bereberes [72]; Moroccans [73]; Western Samoa [74]; Madang [75];

Rabaul [76]; New Caledonia [74]; Fidji [75]; Papua-Nueva Guinea

[76]; Central Desert; [77]; Yuendumu [77]; Kimberley [74]; Cape

York [75]; South American Negroids [33]; North American Negroids

[33]; Hottentots [33]; San (Bushmen) [33]; Ainu [61]; Zuni [33];

NYC Negroids [78]; Bubi [79]; Caucasoids [45]; Choco [45];

Providencia [45]; Senegalese [33]; Wayu (Unpublished); Afrocolom-

bians [65]; Colombian Mestizos

Mol Biol Rep (2011) 38:3689–3701 3695

123

However, sharing of HLA haplotypes may be found

between Amerindians and Polynesians by studying partic-

ularly allele genealogies [44].

Figures 3 and 4 depict a HLA-DRB1, DQB1 NJ tree and

show how the Amerindians are grouped among themselves

and outside of the Na-Dene and Eskimos American groups

and also from the Orientals and Caucasoids. When the

Polynesians, Melanesians, Micronesians and Negroids are

included (see Table 1), the topology of the tree (DRB1

alone) is not changed (Fig. 4). By combining this allele

Fig. 4 Neighbor-Joining (NJ)

dendrogram based on HLA-

DRB1 allele frequencies. The

genetic relatedness among

Amerindians, Na-Dene,

Eskimos, Asians, Negroids,

Europeans and Polynesians are

determined by calculating the

genetic distances between

populations (DA), using HLA-

DRB1 allele frequencies.

Amerindians cluster together

and separated from the rest of

the world populations [15, 65,

67, 68, 78]

3696 Mol Biol Rep (2011) 38:3689–3701

123

frequency studies with particular quasi-specific Amerin-

dian alleles a gene flow may be detected between Amer-

indians and Pacific and other Asian people [15].

HLA-A, -B, -DRB1, DQA1 and DQB1 correspondence

analysis (Fig. 5) and extended haplotypes (Tables 3

and 4) in Jaidukama Amerindians

Correspondence analysis with DRB1 and DQB1 alleles

(Fig. 5) shows that Amerindians constitute a different

cluster from Na-Dene, Eskimo, Siberian, Asian and Cau-

casoid populations. This supports results in dendrograms

(Figs. 3 and 4). Phylogenetic trees and correspondence

analyses results support the hypothesis that Amerindians

have a unique genetic background but with a noticeable

gene flow between them and Asian and Pacific Islanders

[15].

Real extant (not calculated by statistic methods but by

family haplotype segregation) HLA haplotypes were

described for the first time in a small and secluded Amerin-

dian population, due to the possibility to study families:

inheritance pattern (see Tables 3 and 4). The HLA class II

haplotypes found are characteristics of the Amerindian pop-

ulations although some of them appear in non-Amerindian

populations: (a) DRB1*1602-DQA1*0501-DQB1*0301 is

exclusively found in Amerindians [20, 54–57]; (b)

DRB1*0404-DQA1*03011-DQB1*0302 is present in other

Amerindians [20, 55–57], in the Penutian Indians from

British Columbia [58], and in low frequency in Orientals

(Singapore-Chinese, Japanese, Khoton-Mongolian and

Khalk-Mongolian [33, 59]. This suggests a positive gene flow

between Orientals and Amerindians [15]; (c) DRB1*1402-

DQA1*0501-DQB 1*0301 present in other Amerindians [15,

20, 54–57], in the Na-Dene Indians, Eskimos and Siberians in

high frequency [58, 60] and is also found in low frequency in

Orientals [33, 59]; and (d) DRB1*0407-DQA1*03011-DQB

1*0302 present in other Amerindians [20, 54, 56, 57] and in

low frequency in NaDene Indians [58].

On the other hand, DRB1*1406-DQA1*0501-

DQB1*0301 haplotype has previously been described in

Amerindians and in Ainu Asians [20, 57, 61] and

DRB1*0802-DQA1*0401-DQB1*0402 haplotype previ-

ously described in Amerindians, Na-Dene Indians, Eskimos

and Ainu Asians, [20, 54–58, 61] are not present in the Ja-

idukama Amerindians.

Also, the lack of Caucasoid and Negroid haplotypes

reflects the absence of admixture of Jaidukama Amerindi-

ans with other ethnic groups.

The extended haplotypes found in Jaidukama Amerindi-

ans are shown in Table 4. The DRB1*0407-DQA1*03011-

DQB1*0302 class II haplotype was included in several

extended haplotypes with A2-B35, A24-B35, A2-B40, A24-

B40, A24-B39, and A2-B51. Haplotype DRB1*1602-

DQA1*0501-DQB1*0301 was found together with A24-

B40 and A24-B35. Haplotype DQA1*03011-DQB1*0302 is

found with A2-B40, A24-B40, A2-B35, A24-B35 and A2-

B51 and haplotype DRB1*1602-DQA1*0501-DQB1*0301

is observed with A24-B35 and A24-B40.

Some full extended haplotypes (including genetic HLA-A

and B typings) may be the same than these found in Lakota-

Fig. 5 Correspondence analysis

based on HLA-DRB1 and HLA-

DQB1 allele frequencies. The

analysis shows a global view of

the genetic relationships among

Amerindian, Na-Dene, Eskimo,

Asian, Negroid and European

populations according to HLA-

DRB1 and HLA-DQB1 allele

frequencies. These relationships

are calculated in n dimensions

and represented in two

dimensions. Colours represent

an approximate grouping of

populations [15, 65, 67, 68, 78].

(Color figure online)

Mol Biol Rep (2011) 38:3689–3701 3697

123

Sioux [62]. This highlights how the same haplotypes may be

found in North (Lakota-Sioux) and South American Amer-

indians (Jaidukama), probably pointing out the existence of a

founder effect for both North and South Amerindians. Also

the fact that these small Jaidukama group has probably

evolved by having a considerable amount of new specific

extended HLA haplotypes supports that haplotypes may vary

faster than alleles [15]. Data on HLA class I and class II

extended haplotypes studies in Amerindian populations are

now quite complete [15, 47]: 5 out of 17 haplotypes found in

Jaidukama Amerindians have not been previously described

as Amerindians; this is a striking finding. Full HLA haplo-

types may be more important for an efficient immune

response than alleles [63]. Finally, the sharing of this

secluded Jaidukama Amerindians of HLA alleles and DRB1-

DQB1 modules with Asian and Pacific Islanders supports

existence of a gene flow of Amerindians with outside-

America populations [15]. The study of this small and

secluded (until recently) Amerindian groups are not only of

anthropological and immunological interest, but also

important for future transplantation programs and HLA

linked diseases epidemiology studies.

Acknowledgments This work was supported in part by grants from

the Spanish Ministry of Health (FISS PI051039 and PI080838), and

three different Mutua Madrilena Automovilista grants. We are

grateful to the Jaidukama Indian Community, Organizacion Indi-

genista (OIA) and to Programa Aereo de Salud del Servicio Seccional

de Salud de Antioquia.

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