{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:56:58Z","timestamp":1790816218953,"version":"4.1.0"},"reference-count":93,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,5,25]],"date-time":"2018-05-25T00:00:00Z","timestamp":1527206400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100010268","name":"Consejo Nacional para Investigaciones Cient\u00edficas y Tecnol\u00f3gicas","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005298","name":"Universidad de Costa Rica","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005298","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000765","name":"University College London","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000765","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HLA"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:p>The HLA system shows the most extensive polymorphism in the human genome. Allelic and haplotypic frequencies of HLA genes vary dramatically across human populations. Due to a complex history of migration, populations in Latin America show a broad variety of admixture proportions, usually varying not only between countries, but also within countries. Knowledge of HLA allele and haplotype frequencies is essential for medical fields such as transplantation, but also serves as a means to assess genetic diversity and ancestry in human populations. Here, we have determined high\u2010resolution HLA\u2010A, \u2010B, \u2010C, and \u2010DRB1 allele and haplotype frequencies in a sample of 713 healthy subjects from three Mestizo populations, one population of African descent, and Amerindians of five different groups from Costa Rica and Nicaragua and compared their profiles to a large set of indigenous populations from Iberia, Sub\u2010Saharan Africa, and the Americas. Our results show a great degree of allelic and haplotypic diversity within and across these populations, with most extended haplotypes being private. Mestizo populations show alleles and haplotypes of putative European, Amerindian, and Sub\u2010Saharan African origin, albeit with differential proportions. Despite some degree of gene flow, Amerindians and Afro\u2010descendants show great similarity to other Amerindian and West African populations, respectively. This is the first comprehensive study reporting high\u2010resolution HLA diversity in Central America, and its results will shed light into the genetic history of this region while also supporting the development of medical programs for organ and stem cell transplantation.<\/jats:p>","DOI":"10.1111\/tan.13280","type":"journal-article","created":{"date-parts":[[2018,4,24]],"date-time":"2018-04-24T06:55:15Z","timestamp":1524552915000},"page":"514-529","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["High\u2010resolution HLA allele and haplotype frequencies in majority and minority populations of Costa Rica and Nicaragua: Differential admixture proportions in neighboring countries"],"prefix":"10.1111","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3696-5803","authenticated-orcid":false,"given":"E.","family":"Arrieta\u2010Bola\u00f1os","sequence":"first","affiliation":[{"name":"Institute for Experimental Cellular Therapy University Hospital  Essen Germany"},{"name":"Anthony Nolan Research Institute Royal Free Hospital  London UK"},{"name":"Centro de Investigaciones en Hematolog\u00eda y Trastornos Afines (CIHATA) Universidad de Costa Rica  San Jos\u00e9 Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. J.","family":"Madrigal\u2010S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Escuela de Medicina Universidad de Costa Rica  San Jos\u00e9 Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. E.","family":"Stein","sequence":"additional","affiliation":[{"name":"Anthony Nolan Research Institute Royal Free Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"\u00d3rlich\u2010P\u00e9rez","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones en Hematolog\u00eda y Trastornos Afines (CIHATA) Universidad de Costa Rica  San Jos\u00e9 Costa Rica"},{"name":"Divisi\u00f3n de Banco de C\u00e9lulas Madre Laboratorio Cl\u00ednico, Hospital San Juan de Dios  San Jos\u00e9 Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. J.","family":"Moreira\u2010Espinoza","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Morfol\u00f3gicas Universidad Nacional Aut\u00f3noma de Nicaragua  Le\u00f3n Nicaragua"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Paredes\u2010Carias","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Morfol\u00f3gicas Universidad Nacional Aut\u00f3noma de Nicaragua  Le\u00f3n Nicaragua"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Vanegas\u2010Padilla","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Morfol\u00f3gicas Universidad Nacional Aut\u00f3noma de Nicaragua  Le\u00f3n Nicaragua"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Salazar\u2010S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Escuela de Medicina Universidad de Costa Rica  San Jos\u00e9 Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. A.","family":"Madrigal","sequence":"additional","affiliation":[{"name":"Anthony Nolan Research Institute Royal Free Hospital  London UK"},{"name":"Cancer Institute University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. G. E.","family":"Marsh","sequence":"additional","affiliation":[{"name":"Anthony Nolan Research Institute Royal Free Hospital  London UK"},{"name":"Cancer Institute University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. E.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Anthony Nolan Research Institute Royal Free Hospital  London UK"},{"name":"Center for International Blood and Marrow Transplant Research, Department of Medicine Medical College of Wisconsin  Milwaukee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,5,25]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1161"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-1809.2001.6510001.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/iji.12029"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2011.0320"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2016.09.003"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000037"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-05-576041"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000358798"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-005-5081-x"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.06.022"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2011.03438.x"},{"key":"e_1_2_6_13_1","unstructured":"National Nicaraguan Institute of Development Information (INIDE). Poblaci\u00f3n Total estimada al 30 de Junio del a\u00f1o 2012. Sistema Nacional de Estad\u00ecsticas Vitales.2012."},{"key":"e_1_2_6_14_1","unstructured":"Costa Rican National Institute for Statistics and Censuses (INEC). 2011\u20102025. Proyecciones distritales. Poblaci\u00f3n total proyectada por grupos de edades seg\u00fan regi\u00f3n de planificaci\u00f3n y sexo.2015."},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.3378\/027.085.0505"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-1809.2003.00010.x"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.2010.00612.x"},{"issue":"3","key":"e_1_2_6_18_1","first-page":"1237","article-title":"Analysis of various classical genetic markers in the Costa Rica population","volume":"49","author":"Morera B","year":"2001","journal-title":"Rev Biol Trop"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajhb.21110"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013081"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/YPG.0b013e3283202816"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eurpsy.2013.10.001"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2013.4100"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2011-110782"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200704-592OC"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/00041444-200403000-00003"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.comppsych.2011.05.003"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-002-0899-8"},{"issue":"3","key":"e_1_2_6_29_1","first-page":"629","article-title":"Is the Central Valley of Costa Rica a genetic isolate?","volume":"52","author":"Morera B","year":"2004","journal-title":"Rev Biol Trop"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-10-0066"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2008.07.002"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-11-0131"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.30614"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djw300"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2010.10.005"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajpa.1330580213"},{"issue":"1","key":"e_1_2_6_37_1","first-page":"63","article-title":"Microevolution in lower central America: genetic characterization of the Chibcha\u2010speaking groups of Costa Rica and Panama, and a consensus taxonomy based on genetic and linguistic affinity","volume":"46","author":"Barrantes R","year":"1990","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2011.06.002"},{"issue":"5","key":"e_1_2_6_39_1","first-page":"921","article-title":"Maximum\u2010likelihood estimation of molecular haplotype frequencies in a diploid population","volume":"12","author":"Excoffier L","year":"1995","journal-title":"Mol Biol Evol"},{"issue":"2","key":"e_1_2_6_40_1","first-page":"19","article-title":"Using uniformat and gene[rate] to analyze data with ambiguities in population genetics","volume":"11","author":"Nunes JM","year":"2015","journal-title":"Evol Bioinformatics Online"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/tan.12356"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/tan.12160"},{"issue":"5","key":"e_1_2_6_43_1","first-page":"486","article-title":"Cactus, a population genetics analysis environment","volume":"66","author":"Maldonado\u2010Torres H","year":"2005","journal-title":"Tissue Antigens"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2013.06.025"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/139.1.457"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-0998.2010.02847.x"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1166"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2008.05.001"},{"issue":"6","key":"e_1_2_6_49_1","first-page":"371","article-title":"The influence of HLA resolution level on population comparisons strongly depends on loci and geographic ranges","volume":"89","author":"Di D","year":"2017","journal-title":"HLA"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1177\/001316446002000116"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2007.04.005"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/tan.12470"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.5.545"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/tan.13210"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005693"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1086\/324209"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1086\/342295"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20042158"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.2005.00478.x"},{"key":"e_1_2_6_60_1","first-page":"580","volume-title":"Immunobiology of the Human MHC: Proceedings of the 13th International Histocompatibility Workshop and Conference","author":"Mack S","year":"2007"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2017.11.002"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajhb.22382"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1353\/hub.2005.0032"},{"issue":"3","key":"e_1_2_6_64_1","first-page":"379","article-title":"Genetic diversity and racial mixture in Amerindians from Costa Rica and Panama","volume":"41","author":"Barrantes R","year":"1993","journal-title":"Rev Biol Trop"},{"issue":"2","key":"e_1_2_6_65_1","first-page":"249","article-title":"Genetic variation in the Bribri and Cabecar Amerindians from Talamanca, Costa Rica","volume":"39","author":"Azofeifa J","year":"1991","journal-title":"Rev Biol Trop"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8644(200102)114:2<99::AID-AJPA1010>3.0.CO;2-V"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0030185"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11258"},{"issue":"1","key":"e_1_2_6_69_1","first-page":"123","article-title":"Demography and genetics of a Guaymi Amerindian population of Limoncito, Costa Rica","volume":"29","author":"Barrantes R","year":"1981","journal-title":"Rev Biol Trop"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0039.1999.540601.x"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0198-8859(01)00212-9"},{"key":"e_1_2_6_72_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0074442"},{"issue":"1","key":"e_1_2_6_73_1","first-page":"160","article-title":"Analysis of HLA class II haplotypes in the Cayapa Indians of Ecuador: a novel DRB1 allele reveals evidence for convergent evolution and balancing selection at position 86","volume":"55","author":"Titus\u2010Trachtenberg EA","year":"1994","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-5223.1997.00019.x"},{"key":"e_1_2_6_75_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.105.052837"},{"key":"e_1_2_6_76_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.13-1308"},{"key":"e_1_2_6_77_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-010-0803-x"},{"key":"e_1_2_6_78_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajpa.23347"},{"key":"e_1_2_6_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchb.2014.08.005"},{"key":"e_1_2_6_80_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013336"},{"key":"e_1_2_6_81_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajhb.23055"},{"key":"e_1_2_6_82_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajpa.21355"},{"key":"e_1_2_6_83_1","first-page":"39","article-title":"Estimacion de la mezcla gen\u00e9tica en la poblaci\u00f3n de Nicaragua","volume":"16","author":"Morera B","year":"2006","journal-title":"Cuadernos de Antropolog\u00eda"},{"key":"e_1_2_6_84_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0135960"},{"key":"e_1_2_6_85_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00197169"},{"issue":"1","key":"e_1_2_6_86_1","first-page":"12","article-title":"Polymorphism of erythrocytic glucose\u20106\u2010phosphate dehydrogenase in Costa Rica","volume":"33","author":"Chaves M","year":"1988","journal-title":"Sangre (Barc)"},{"issue":"4","key":"e_1_2_6_87_1","first-page":"95","article-title":"Las hemoglobinopat\u00edas en Costa Rica. Aspectos hist\u00f3ricos, culturales y epidemiol\u00f3gicos","volume":"7","author":"S\u00e1enz G","year":"1986","journal-title":"Rev Costarricense Cien Med"},{"key":"e_1_2_6_88_1","doi-asserted-by":"publisher","DOI":"10.1590\/S1020-49891998000100001"},{"issue":"2","key":"e_1_2_6_89_1","first-page":"361","article-title":"Hemoglobinopathies in Caribbean Basin countries","volume":"36","author":"Saenz Renauld GF","year":"1988","journal-title":"Rev Biol Trop"},{"issue":"1","key":"e_1_2_6_90_1","first-page":"42","article-title":"Abnormal hemoglobins and thalassemias in Costa Rica, other countries of Central America, and Panama","volume":"22","author":"Saenz GF","year":"1988","journal-title":"Bull Pan Am Health Organ"},{"key":"e_1_2_6_91_1","volume-title":"Migraciones internas en Costa Rica","author":"Jim\u00e9nez\u2010Castro W","year":"1956"},{"key":"e_1_2_6_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2014.09.011"},{"key":"e_1_2_6_93_1","unstructured":"Costa Rican National Institute for Statistics and Censuses (INEC). Censo 2011. Indicadores \u00e9tnico\u2010raciales seg\u00fan cant\u00f3n 2011.http:\/\/wwwinecgocr\/censos\/censos-2011. Accessed May 28 2017."},{"key":"e_1_2_6_94_1","volume-title":"Total de nacimientos por nacionalidad de la madre, seg\u00fan pa\u00eds de origen de la madre","author":"Costa Rican National Institute for Statistics and Censuses (INEC)","year":"2000"}],"container-title":["HLA"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Ftan.13280","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/tan.13280","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T18:28:52Z","timestamp":1695493732000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/tan.13280"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,25]]},"references-count":93,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["10.1111\/tan.13280"],"URL":"https:\/\/doi.org\/10.1111\/tan.13280","archive":["Portico"],"relation":{},"ISSN":["2059-2302","2059-2310"],"issn-type":[{"value":"2059-2302","type":"print"},{"value":"2059-2310","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,25]]},"assertion":[{"value":"2017-05-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}