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MHC DQA1 allele frequencies in Colombia
62
P329
Abstracts
P330
HLA DIFFERENTIATION AMONG MESOAMERICAN NATIVES
DNA PROFILE OF CLASS" LOCIIN SERIS:A MEXICAN INDIANTRIBE
Hollenbach JA, Barcellos LF, Thomson G, Winkler C, Winter M, Klitz W Univ. of California, Berkeley, Nat. Cancer Inst., Frederick, MD, USA and Inst. Nat. de Antropologia e Historia, Oaxaca, Mexico
Debaz Hector", Alaez Carmen*, Olivo Angelica*, Pujol M. Janette.., Duran Constanza", NavarroJose L", JuarezVictor", Gorodezky Clara*. *Dept. of Immunogenetics, INORE; Mexico City; ..Public Health Lab. Sonora. Mexico.
Three Amerindian populations from Oaxaca, Mexico, the Zapotec (n",75), Mixtec Alta (n",103) and Mixe (n",55), were typed for four HLA class II loci using PCR-SSOP methods. The alleles present in these populations reveal lillie or no admixture with European or African sources. In all three groups ORB1, DOA1 and DOB1 allele frequency distributions are consistently more even than neutrality expectations, while the DPBl distributions are less even. At all loci a reduction in the level of class II polymorphism was observed, as has been described for other Amerindians. This was countered by an impressive degree of DR-DO haplotype diversity, with many previously unknown haplotypes detected using standard methods for haplotype estimation. Despite their common origin the three populations present clear evidence of HLA differentiation. Certain alleles at each of the four loci are seen in only one of the populations, and those shared often have markedly varying frequencies. Furthermore, each population possesses a number of haplotypes uniquely its own, often with significant disequilibrium present across the four-locus haplotype. Evolutionary forces have operated in the HLA class II region to achieve conspicuous divergence between three populations possessing recent common ancestry and a relatively small complement of founding alleles.
The knowledge of the genetic structure of the MHC complex in isolated populetions may provide answers to their origins, the impact of genetics on epidemiology and to the understanding of humandiversity. The Seris selected for this study are composed by 619 individuals belonging to the HokanoCoahuiUeca linguistic family and preserve their cultural identity; They inhabit the coast of the State of Sonorain the northwestof Mexico. We included101 members of 26 families. They suffer mainly of infections, hypertension, rlleumaticdis. and type II diabetes. The studywas done within the frame of the 12thW usingthe protocols, primersand probes designedfor the 11th and 12th Ws. DNA typing was done using PCR-SSO and SSPs. Family segregation demonstarted the presence of only 7 haplotypes: DRB1*0407-DQA1*03011OOB1*0302 (90%); DRBl *0802-DQA1-*0401-OOBl*0402 (73%); and DRB1*1402-DQA1*0501-DQB1*0301(27%). One ORBI *0404; (7) *0701, (1) *1101 and (1)*0101 haplotypes of Mestizo or Caucasian origin were present. The reduction of diversity, the loss of the ORB1*1602 haplotype and of some OR4alleles presentin other Indians, is consistent with a bottleneck effect. The genetic profile is very close to that of the western USA Indians, but different from MexicanMayansor some SouthAmerindians, suggesting that selection may havebeenan importantmechanism. The geneticdifference betweenSeris and others, emphasizes the importance of analysing carefullyeach population to unravelthe interactions between genesand environment.
P331
FREQUENCY Of THE DQjlI* AND DQaI' GENOTYPEIN PUERTO RICANS (PR). A. SaDIiago, L. GoII7U:l, R \lull, J. Dorman, M. Trucco, M. Serruro-Rios and T. Frazer-Liado. PooceScbooIofModicD:,Pooce,PR,MSU, E. Lansing, MI, UDiv. of Pittsburgh, Pittsburgh, PA, UDiversidad Complutense, Madrid, Spain. Worldwide iDcidenoe of 100M varies between 1-40 casesllO' ebildreulyr in differenlethnic group' and geognpbioal areas. PR is a moderaterisk locationwith an incidenceof 15-18110'. However, it is .... bigbest risk locationof .... Caribbean and Latin America, ..... iDcideaoe 4.VI0',and 1.5foldhigherthan Modrid,I \.3110', PR'. major population of origin. Toddermine effcotsof HLA DQ geneson .... inoidenceof 100M, we subtyped DQ loci in 84 COIIbOIs and 87diabetios, random1y selectedfrom a diabetioregisby of865oases,by PCRJDNA probes. The(!OIIOIypeDQllI 002011jl100302 was moreftequeotindiabetiosthanOODlrols (28:1). DQjll0030VDQjll00302 was 5 times higher, and DQjlI0020 11DQtI100201 was 3 timesmore frequent. DQIlI*0602, a proteolive gene, was 8 times more frequeal in oootrolsthandiabetics. Diabelogeaio DQuI' _ , 0501 and 0301, were2 times higherinpatieats, wbiIeDQuI'0201, a proteolive gene, was 3 foldmore frequenlin oootrols. Compared 10 both Spanish and Caooasiao lIOD-diabetic popu\alions, PR frequenoies of " (l)bl and mot< live (P) ...... weresimilar: diabetogemo Caucasiu DO PR Suaoisb 0.24 810020 IDb 0.19 0.22 0.09 81'0302Db 0.16 0.11 0.13 81*0602P 0.09 0.1 0.12 0.27 0.17 "IOOJOIDb 0.16 0.15 0.55 ,,1'40IDb 0.28 ,,100501Db 0.16 0.0 In oooelusion, higher inoidenceof IDDMm PRmay DOl be attributable to markeddiffOl'OllOOS in diabelogeoio or proteolive genes. In addition 10 HLA-DQ,we speoulatevariatiooin incidence resu1ts from otberfOOlon, suoh as otberHLA loci, genes, and/or sooioeoooomic deve\opmeol.
P333
HLA ANTIGENS AND GENE DISTRIBUTION IN SAN BASILIO (SB) AN ISOLATED BLACK POPULATION OF COLOMBIA. S. Jimenez, B. Martinez, M Hernandez, L. Caraballo.
InstituteofImmunological Research, UniversityofCartagena, Colombia Knowledge of the genetic composition and the places of origin of the descendanls of the black African population, that enteredAmerica duringthe slavetrade,is of great scientific interest. SocioanthropologicaJ andlinguistic studies classify thepopulation of SB (a village of 3000 inhabitantslocatednear Cartagena)as African descendants, but there is no genetic analysis that can support this evaluation. In this work we studiedthe lILA classI andII alleles in 119nonrelated subjects from SB, using serologicaland PCR/SSa methods. Most frequentclassI antigens were A23, 28, 30, 33; B35, 42, 51, 58, 53, 70 and C2, 4, 7. Comparingthe number of significant differencesbetweenthe antigenic frequencies of SB populationandthose studiedin the 11th IHW and mulattos from Cartagena (Tissue Antigens 1992;39:128-133) we found a greater numberof differences with mulattos than with African populations, specially with that grouped in the 11th IHW as "West Africa." The most frequent class II genes were: DRBl*0301, 1501, 1201, 1101, 0302, 070; DQAl'0102, 0101, 0501; DQBl'0501, 06, 0301; DPAl'0401, 02A; DPBl*0101, 0401,2501, 1801. Theseresults, aswell asclassI andclass II haplotype distribution, are close to those from black African populations, suggesting that SB population was originated mainly from West-Africa.
P332
A NOVEL HLA-B3S AlLELE (B*3510) FOUND IN ISOLATED JAIDUKAMA COLOMBIAN AMERICAN INDIANS
Eduardo Gomez-Casado, Fabiola Montoya", Jorge Martinez-Lase, Nieves DiazCampos,Claudia 1. Bedoya",Pilar Varela, AntonioAmaiz-Villena. Department of Immunology, Hospital 12 de Octubre, Universidad Complutense, Madrid,Spain. ..Sectionof lrnmunology. Corporacionpara Investigaciones Biol6gicas (eIB), Medellin, Colombia. It has been carried out an RIA study in a North Western Colombiantribe (Antioquiaregion),the Jaidukama, of caribbean descent and language.Self-sufficient family groupsdwellin the middleof a hillyrain forest in open hut/houses, and contact withcivilization is minimal,mainlyconsisting of helicoptervisits by health care workers. A newB35allele has been foundin 3 unrelated individuals. ThisnewJaidukama allele (B*3510) is identicalto the B*3501 allele exceptat codon63 that showsa changefrom Asparagine (Asn) to Glutamic acid [Glu), which has varied a neutral polarity to a negative charge at this site. Glu at 63 residue is only present in B*3513and B""3516 SUbtypes and is the one change found in the a1 helix part of B35 molecules; also Glutamic acid at 63 residue is close to Pi and lies 4.0 A apart from the P2 amide nitrogen.It willcertainlymodify the N-terminalinteractionsof B35J aidukamamolecule with the N-terminusof differentpeptides. However,the Asn/Glu polymorphism at 63 residue is preserved, as seen in other class I molecules. The pressure to maintain Asn/Glupolymorphism at residue63 maybe due to the existenceof differentpathogens drivingit accordingto characteristicenvironments. Isolation among South American tribes maybe a goodexample to studythis evolutionary model; this isolationwas even more pronounced after the Spanish invasion 'bottleneck', when about 60-80000000 indiansdied (1500-1600 y. AD1 mostlybecause contact with new pathogens. B*4801 and B*1504have also been found in other American Indian populationsand may be the codon 63 (GAG) allele donors to B*3501 (also found in Asians and American Indians) that resulted in the B*3510 Jaidukama molecule.
P334
MHC DQAl ALLELE FREQUENCIES IN COLOMBIA.
JuanJ. Yunis, Alfonso Suarez, Humberto Ossa, Alexander Garcia andEmilio Yunis. Instituto de Genetica, Universidad Nacional de Colombia,Bogota,D.C.Colombia. We haveanalyzed 2225samples from606Colombian families for MHC DQA1 alleles by PCRamplification followed by hybridization withDigoxigenin-Iabeled SSOPanddetection by a chemiluminescent method (Genius, Boehringer Mannheim,lndianapolis,IN). Segregation analysis of DQAl alleles withinfamilies was cameoout In orderto avoidduplication of results. A totalof 2408DQAl alleleswere infonnative. Theaverage frequency of DQA1 alleles in Colombia is presented in the table below' DQA1 ALLELE 0101 0102 0103 0201 03 0401 0501
FREQUENCY
NUMBER
13.29 12.54 6.27 12.33 26.45 6.81 2230
320 302 151 297 637 164 537
Somedifferences weredetected when analyzed by region, it's signification will be discussed faced to dataobtained for blood groups. These results will be important for transplantation studies aswellasto generate a database to be used in forensics andpaternity testing studies
P329
Abstracts
P330
HLA DIFFERENTIATION AMONG MESOAMERICAN NATIVES
DNA PROFILE OF CLASS" LOCIIN SERIS:A MEXICAN INDIANTRIBE
Hollenbach JA, Barcellos LF, Thomson G, Winkler C, Winter M, Klitz W Univ. of California, Berkeley, Nat. Cancer Inst., Frederick, MD, USA and Inst. Nat. de Antropologia e Historia, Oaxaca, Mexico
Debaz Hector", Alaez Carmen*, Olivo Angelica*, Pujol M. Janette.., Duran Constanza", NavarroJose L", JuarezVictor", Gorodezky Clara*. *Dept. of Immunogenetics, INORE; Mexico City; ..Public Health Lab. Sonora. Mexico.
Three Amerindian populations from Oaxaca, Mexico, the Zapotec (n",75), Mixtec Alta (n",103) and Mixe (n",55), were typed for four HLA class II loci using PCR-SSOP methods. The alleles present in these populations reveal lillie or no admixture with European or African sources. In all three groups ORB1, DOA1 and DOB1 allele frequency distributions are consistently more even than neutrality expectations, while the DPBl distributions are less even. At all loci a reduction in the level of class II polymorphism was observed, as has been described for other Amerindians. This was countered by an impressive degree of DR-DO haplotype diversity, with many previously unknown haplotypes detected using standard methods for haplotype estimation. Despite their common origin the three populations present clear evidence of HLA differentiation. Certain alleles at each of the four loci are seen in only one of the populations, and those shared often have markedly varying frequencies. Furthermore, each population possesses a number of haplotypes uniquely its own, often with significant disequilibrium present across the four-locus haplotype. Evolutionary forces have operated in the HLA class II region to achieve conspicuous divergence between three populations possessing recent common ancestry and a relatively small complement of founding alleles.
The knowledge of the genetic structure of the MHC complex in isolated populetions may provide answers to their origins, the impact of genetics on epidemiology and to the understanding of humandiversity. The Seris selected for this study are composed by 619 individuals belonging to the HokanoCoahuiUeca linguistic family and preserve their cultural identity; They inhabit the coast of the State of Sonorain the northwestof Mexico. We included101 members of 26 families. They suffer mainly of infections, hypertension, rlleumaticdis. and type II diabetes. The studywas done within the frame of the 12thW usingthe protocols, primersand probes designedfor the 11th and 12th Ws. DNA typing was done using PCR-SSO and SSPs. Family segregation demonstarted the presence of only 7 haplotypes: DRB1*0407-DQA1*03011OOB1*0302 (90%); DRBl *0802-DQA1-*0401-OOBl*0402 (73%); and DRB1*1402-DQA1*0501-DQB1*0301(27%). One ORBI *0404; (7) *0701, (1) *1101 and (1)*0101 haplotypes of Mestizo or Caucasian origin were present. The reduction of diversity, the loss of the ORB1*1602 haplotype and of some OR4alleles presentin other Indians, is consistent with a bottleneck effect. The genetic profile is very close to that of the western USA Indians, but different from MexicanMayansor some SouthAmerindians, suggesting that selection may havebeenan importantmechanism. The geneticdifference betweenSeris and others, emphasizes the importance of analysing carefullyeach population to unravelthe interactions between genesand environment.
P331
FREQUENCY Of THE DQjlI* AND DQaI' GENOTYPEIN PUERTO RICANS (PR). A. SaDIiago, L. GoII7U:l, R \lull, J. Dorman, M. Trucco, M. Serruro-Rios and T. Frazer-Liado. PooceScbooIofModicD:,Pooce,PR,MSU, E. Lansing, MI, UDiv. of Pittsburgh, Pittsburgh, PA, UDiversidad Complutense, Madrid, Spain. Worldwide iDcidenoe of 100M varies between 1-40 casesllO' ebildreulyr in differenlethnic group' and geognpbioal areas. PR is a moderaterisk locationwith an incidenceof 15-18110'. However, it is .... bigbest risk locationof .... Caribbean and Latin America, ..... iDcideaoe 4.VI0',and 1.5foldhigherthan Modrid,I \.3110', PR'. major population of origin. Toddermine effcotsof HLA DQ geneson .... inoidenceof 100M, we subtyped DQ loci in 84 COIIbOIs and 87diabetios, random1y selectedfrom a diabetioregisby of865oases,by PCRJDNA probes. The(!OIIOIypeDQllI 002011jl100302 was moreftequeotindiabetiosthanOODlrols (28:1). DQjll0030VDQjll00302 was 5 times higher, and DQjlI0020 11DQtI100201 was 3 timesmore frequent. DQIlI*0602, a proteolive gene, was 8 times more frequeal in oootrolsthandiabetics. Diabelogeaio DQuI' _ , 0501 and 0301, were2 times higherinpatieats, wbiIeDQuI'0201, a proteolive gene, was 3 foldmore frequenlin oootrols. Compared 10 both Spanish and Caooasiao lIOD-diabetic popu\alions, PR frequenoies of " (l)bl and mot< live (P) ...... weresimilar: diabetogemo Caucasiu DO PR Suaoisb 0.24 810020 IDb 0.19 0.22 0.09 81'0302Db 0.16 0.11 0.13 81*0602P 0.09 0.1 0.12 0.27 0.17 "IOOJOIDb 0.16 0.15 0.55 ,,1'40IDb 0.28 ,,100501Db 0.16 0.0 In oooelusion, higher inoidenceof IDDMm PRmay DOl be attributable to markeddiffOl'OllOOS in diabelogeoio or proteolive genes. In addition 10 HLA-DQ,we speoulatevariatiooin incidence resu1ts from otberfOOlon, suoh as otberHLA loci, genes, and/or sooioeoooomic deve\opmeol.
P333
HLA ANTIGENS AND GENE DISTRIBUTION IN SAN BASILIO (SB) AN ISOLATED BLACK POPULATION OF COLOMBIA. S. Jimenez, B. Martinez, M Hernandez, L. Caraballo.
InstituteofImmunological Research, UniversityofCartagena, Colombia Knowledge of the genetic composition and the places of origin of the descendanls of the black African population, that enteredAmerica duringthe slavetrade,is of great scientific interest. SocioanthropologicaJ andlinguistic studies classify thepopulation of SB (a village of 3000 inhabitantslocatednear Cartagena)as African descendants, but there is no genetic analysis that can support this evaluation. In this work we studiedthe lILA classI andII alleles in 119nonrelated subjects from SB, using serologicaland PCR/SSa methods. Most frequentclassI antigens were A23, 28, 30, 33; B35, 42, 51, 58, 53, 70 and C2, 4, 7. Comparingthe number of significant differencesbetweenthe antigenic frequencies of SB populationandthose studiedin the 11th IHW and mulattos from Cartagena (Tissue Antigens 1992;39:128-133) we found a greater numberof differences with mulattos than with African populations, specially with that grouped in the 11th IHW as "West Africa." The most frequent class II genes were: DRBl*0301, 1501, 1201, 1101, 0302, 070; DQAl'0102, 0101, 0501; DQBl'0501, 06, 0301; DPAl'0401, 02A; DPBl*0101, 0401,2501, 1801. Theseresults, aswell asclassI andclass II haplotype distribution, are close to those from black African populations, suggesting that SB population was originated mainly from West-Africa.
P332
A NOVEL HLA-B3S AlLELE (B*3510) FOUND IN ISOLATED JAIDUKAMA COLOMBIAN AMERICAN INDIANS
Eduardo Gomez-Casado, Fabiola Montoya", Jorge Martinez-Lase, Nieves DiazCampos,Claudia 1. Bedoya",Pilar Varela, AntonioAmaiz-Villena. Department of Immunology, Hospital 12 de Octubre, Universidad Complutense, Madrid,Spain. ..Sectionof lrnmunology. Corporacionpara Investigaciones Biol6gicas (eIB), Medellin, Colombia. It has been carried out an RIA study in a North Western Colombiantribe (Antioquiaregion),the Jaidukama, of caribbean descent and language.Self-sufficient family groupsdwellin the middleof a hillyrain forest in open hut/houses, and contact withcivilization is minimal,mainlyconsisting of helicoptervisits by health care workers. A newB35allele has been foundin 3 unrelated individuals. ThisnewJaidukama allele (B*3510) is identicalto the B*3501 allele exceptat codon63 that showsa changefrom Asparagine (Asn) to Glutamic acid [Glu), which has varied a neutral polarity to a negative charge at this site. Glu at 63 residue is only present in B*3513and B""3516 SUbtypes and is the one change found in the a1 helix part of B35 molecules; also Glutamic acid at 63 residue is close to Pi and lies 4.0 A apart from the P2 amide nitrogen.It willcertainlymodify the N-terminalinteractionsof B35J aidukamamolecule with the N-terminusof differentpeptides. However,the Asn/Glu polymorphism at 63 residue is preserved, as seen in other class I molecules. The pressure to maintain Asn/Glupolymorphism at residue63 maybe due to the existenceof differentpathogens drivingit accordingto characteristicenvironments. Isolation among South American tribes maybe a goodexample to studythis evolutionary model; this isolationwas even more pronounced after the Spanish invasion 'bottleneck', when about 60-80000000 indiansdied (1500-1600 y. AD1 mostlybecause contact with new pathogens. B*4801 and B*1504have also been found in other American Indian populationsand may be the codon 63 (GAG) allele donors to B*3501 (also found in Asians and American Indians) that resulted in the B*3510 Jaidukama molecule.
P334
MHC DQAl ALLELE FREQUENCIES IN COLOMBIA.
JuanJ. Yunis, Alfonso Suarez, Humberto Ossa, Alexander Garcia andEmilio Yunis. Instituto de Genetica, Universidad Nacional de Colombia,Bogota,D.C.Colombia. We haveanalyzed 2225samples from606Colombian families for MHC DQA1 alleles by PCRamplification followed by hybridization withDigoxigenin-Iabeled SSOPanddetection by a chemiluminescent method (Genius, Boehringer Mannheim,lndianapolis,IN). Segregation analysis of DQAl alleles withinfamilies was cameoout In orderto avoidduplication of results. A totalof 2408DQAl alleleswere infonnative. Theaverage frequency of DQA1 alleles in Colombia is presented in the table below' DQA1 ALLELE 0101 0102 0103 0201 03 0401 0501
FREQUENCY
NUMBER
13.29 12.54 6.27 12.33 26.45 6.81 2230
320 302 151 297 637 164 537
Somedifferences weredetected when analyzed by region, it's signification will be discussed faced to dataobtained for blood groups. These results will be important for transplantation studies aswellasto generate a database to be used in forensics andpaternity testing studies