{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T23:21:07Z","timestamp":1768519267837,"version":"3.49.0"},"posted":{"date-parts":[[2024,12,7]]},"group-title":"Genomics","reference-count":89,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,12,7]],"date-time":"2024-12-07T00:00:00Z","timestamp":1733529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,12,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Killer-cell immunoglobulin-like receptors (\n                  <jats:italic>KIR<\/jats:italic>\n                  s) are essential components of the innate immune system found on the surfaces of natural killer (NK) cells. The\n                  <jats:italic>KIR<\/jats:italic>\n                  s encoding genes are located on chromosome 19q13.4 and are genetically diverse across populations.\n                  <jats:italic>KIR<\/jats:italic>\n                  s are associated with various disease states including HIV progression, and are linked to transplantation rejection and reproductive success. However, there is limited knowledge on the diversity of\n                  <jats:italic>KIR<\/jats:italic>\n                  s from Uganda and Botswana HIV-infected paediatric cohorts, with high endemic HIV rates. We used next-generation sequencing technologies on 312 (246 Uganda, 66 Botswana) samples to generate\n                  <jats:italic>KIR<\/jats:italic>\n                  allele data and employed customised bioinformatics techniques for allelic, allotype and disease association analysis. We show that these sample sets from Botswana and Uganda have different KIRs of different diversities. In Uganda, we observed 147 vs 111 alleles in the Botswana cohort, which had a more than 1 % frequency. We also found significant deviation towards homozygosity for the\n                  <jats:italic>KIR3DL2<\/jats:italic>\n                  gene for both rapid (RPs) and long-term non-progressors (LTNPs)in the Ugandan cohort. The frequency of the bw4-80I ligand was also significantly higher among the LTNPs than RPs (8.9 % Vs 2.0%, P-value: 0.032). In the Ugandan cohort,\n                  <jats:italic>KIR2DS4*001<\/jats:italic>\n                  (OR: 0.671, 95 % CI: 0.481-0.937, FDR adjusted Pc=0.142) and\n                  <jats:italic>KIR2DS4*006<\/jats:italic>\n                  (OR: 2.519, 95 % CI: 1.085-5.851, FDR adjusted Pc=0.142) were not associated with HIV disease progression after adjustment for multiple testing. Our study results provide additional knowledge of the genetic diversity of\n                  <jats:italic>KIR<\/jats:italic>\n                  s in African populations and provide evidence that will inform future immunogenetics studies concerning human disease susceptibility, evolution and host immune responses.\n                <\/jats:p>","DOI":"10.1101\/2024.12.03.626612","type":"posted-content","created":{"date-parts":[[2024,12,7]],"date-time":"2024-12-07T19:10:13Z","timestamp":1733598613000},"source":"Crossref","is-referenced-by-count":0,"title":["High KIR diversity in Uganda and Botswana children living with HIV"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9208-0313","authenticated-orcid":false,"given":"John","family":"Mukisa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Kyobe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marion","family":"Amujal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Katagirya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thabo","family":"Diphoko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaseene","family":"Sebetso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Savannah","family":"Mwesigwa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8445-9414","authenticated-orcid":false,"given":"Gerald","family":"Mboowa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaone","family":"Retshabile","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lesedi","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Busisiwe","family":"Mlotshwa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mogomotsi","family":"Matshaba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daudi","family":"Jjingo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David P.","family":"Kateete","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moses L.","family":"Joloba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graeme","family":"Mardon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil","family":"Hanchard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill A.","family":"Hollenbach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024121000212836000_2024.12.03.626612v1.1","unstructured":"Carrington M , Norman P . The KIR gene Cluster. National Center for Biotechnology Information (US) 2003."},{"key":"2024121000212836000_2024.12.03.626612v1.2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-03-416867"},{"key":"2024121000212836000_2024.12.03.626612v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(00)00242-9"},{"key":"2024121000212836000_2024.12.03.626612v1.4","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.5.2767"},{"key":"2024121000212836000_2024.12.03.626612v1.5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.080588597"},{"key":"2024121000212836000_2024.12.03.626612v1.6","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.092501.134942"},{"key":"2024121000212836000_2024.12.03.626612v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/nri3370"},{"key":"2024121000212836000_2024.12.03.626612v1.8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2009.03208.x"},{"key":"2024121000212836000_2024.12.03.626612v1.9","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200425743"},{"key":"2024121000212836000_2024.12.03.626612v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.06.023"},{"key":"2024121000212836000_2024.12.03.626612v1.11","doi-asserted-by":"publisher","DOI":"10.1007\/s00251-019-01133-w"},{"key":"2024121000212836000_2024.12.03.626612v1.12","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp538"},{"key":"2024121000212836000_2024.12.03.626612v1.13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.583013"},{"key":"2024121000212836000_2024.12.03.626612v1.14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906051106"},{"key":"2024121000212836000_2024.12.03.626612v1.15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047491"},{"key":"2024121000212836000_2024.12.03.626612v1.16","doi-asserted-by":"publisher","DOI":"10.1007\/s002510000281"},{"key":"2024121000212836000_2024.12.03.626612v1.17","doi-asserted-by":"publisher","DOI":"10.1007\/s00251-014-0794-1"},{"key":"2024121000212836000_2024.12.03.626612v1.18","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20051884"},{"key":"2024121000212836000_2024.12.03.626612v1.19","doi-asserted-by":"publisher","DOI":"10.1007\/s00251-012-0629-x"},{"key":"2024121000212836000_2024.12.03.626612v1.20","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.674778"},{"issue":"4","key":"2024121000212836000_2024.12.03.626612v1.21","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1111\/imm.13289","article-title":"The combinatorial diversity of KIR and HLA class I allotypes in Peninsular Malaysia","volume":"162","year":"2021","journal-title":"Immunology"},{"key":"2024121000212836000_2024.12.03.626612v1.22","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msab053"},{"key":"2024121000212836000_2024.12.03.626612v1.23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00556"},{"key":"2024121000212836000_2024.12.03.626612v1.24","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msab298"},{"key":"2024121000212836000_2024.12.03.626612v1.25","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1801586"},{"key":"2024121000212836000_2024.12.03.626612v1.26","doi-asserted-by":"crossref","unstructured":"Norman PJ , Hollenbach JA , Nemat-Gorgani N , et al. Co-evolution of human leukocyte antigen (HLA) class I ligands with killer-cell immunoglobulin-like receptors (KIR) in a genetically diverse population of sub-Saharan Africans. PLoS genetics. 2013;9(10).","DOI":"10.1371\/journal.pgen.1003938"},{"key":"2024121000212836000_2024.12.03.626612v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2015.03.002"},{"key":"2024121000212836000_2024.12.03.626612v1.28","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2018.0147"},{"key":"2024121000212836000_2024.12.03.626612v1.29","doi-asserted-by":"publisher","DOI":"10.1111\/tan.15177"},{"key":"2024121000212836000_2024.12.03.626612v1.30","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2859-7"},{"key":"2024121000212836000_2024.12.03.626612v1.31","doi-asserted-by":"publisher","DOI":"10.1038\/nature13997"},{"key":"2024121000212836000_2024.12.03.626612v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.01.042"},{"key":"2024121000212836000_2024.12.03.626612v1.33","doi-asserted-by":"crossref","unstructured":"Kyobe S , Mwesigwa S , Kisitu GP , et al. Exome Sequencing Reveals a Putative Role for HLA-C*03:02 in Control of HIV-1 in African Pediatric Populations. Frontiers in Genetics. 2021;12(1586).","DOI":"10.3389\/fgene.2021.720213"},{"key":"2024121000212836000_2024.12.03.626612v1.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.03.010"},{"key":"2024121000212836000_2024.12.03.626612v1.35","doi-asserted-by":"publisher","DOI":"10.1007\/s00251-013-0724-7"},{"key":"2024121000212836000_2024.12.03.626612v1.36","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-021-03652-y"},{"key":"2024121000212836000_2024.12.03.626612v1.37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1008904"},{"issue":"4","key":"2024121000212836000_2024.12.03.626612v1.38","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1111\/imm.12802","article-title":"Killer-cell immunoglobulin-like receptors on the cusp of modern immunogenetics","volume":"152","year":"2017","journal-title":"Immunology"},{"key":"2024121000212836000_2024.12.03.626612v1.39","doi-asserted-by":"publisher","DOI":"10.1038\/srep42470"},{"key":"2024121000212836000_2024.12.03.626612v1.40","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-13-405"},{"key":"2024121000212836000_2024.12.03.626612v1.41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0151364"},{"key":"2024121000212836000_2024.12.03.626612v1.42","unstructured":"Janeway Jr C TP , Walport M . Immunobiology: The immune system in health and disease. Principles of innate and adaptive immunity 2001."},{"key":"2024121000212836000_2024.12.03.626612v1.43","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00256-09"},{"issue":"7","key":"2024121000212836000_2024.12.03.626612v1.44","first-page":"333","article-title":"Role of combination NK\/KIRs in the natural history of viral infections","volume":"108","year":"2017","journal-title":"Recenti progressi in medicina"},{"key":"2024121000212836000_2024.12.03.626612v1.45","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gene.6364256"},{"key":"2024121000212836000_2024.12.03.626612v1.46","doi-asserted-by":"crossref","unstructured":"Tukwasibwe S , Nakimuli A , Traherne J , et al. Variations in killer-cell immunoglobulin-like receptor and human leukocyte antigen genes and immunity to malaria. Cellular & Molecular Immunology. 2020:1\u20138.","DOI":"10.1038\/s41423-020-0482-z"},{"key":"2024121000212836000_2024.12.03.626612v1.47","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2000144"},{"issue":"1","key":"2024121000212836000_2024.12.03.626612v1.48","first-page":"1","article-title":"Genotype B of killer cell immunoglobulin-like receptor is related with gastric cancer lesions","volume":"8","year":"2018","journal-title":"Scientific reports"},{"key":"2024121000212836000_2024.12.03.626612v1.49","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.02022"},{"key":"2024121000212836000_2024.12.03.626612v1.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2008.07.004"},{"key":"2024121000212836000_2024.12.03.626612v1.51","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.2.647"},{"key":"2024121000212836000_2024.12.03.626612v1.52","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.8.5222"},{"key":"2024121000212836000_2024.12.03.626612v1.53","doi-asserted-by":"publisher","DOI":"10.1186\/s41231-023-00141-z"},{"key":"2024121000212836000_2024.12.03.626612v1.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.11.052"},{"key":"2024121000212836000_2024.12.03.626612v1.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2023.11.030"},{"key":"2024121000212836000_2024.12.03.626612v1.56","doi-asserted-by":"publisher","DOI":"10.1038\/s41525-021-00185-w"},{"key":"2024121000212836000_2024.12.03.626612v1.57","doi-asserted-by":"publisher","DOI":"10.1086\/521165"},{"issue":"1","key":"2024121000212836000_2024.12.03.626612v1.58","first-page":"752312","article-title":"Pediatric HIV Long-Term Nonprogressors","volume":"2014","year":"2014","journal-title":"Case reports in infectious diseases"},{"key":"2024121000212836000_2024.12.03.626612v1.59","doi-asserted-by":"publisher","DOI":"10.1111\/tan.14949"},{"key":"2024121000212836000_2024.12.03.626612v1.60","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz950"},{"key":"2024121000212836000_2024.12.03.626612v1.61","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-8286.2005.01155.x"},{"key":"2024121000212836000_2024.12.03.626612v1.62","doi-asserted-by":"crossref","unstructured":"Guo SW , Thompson EA . Performing the exact test of Hardy-Weinberg proportion for multiple alleles. Biometrics. 1992:361\u2013372.","DOI":"10.2307\/2532296"},{"key":"2024121000212836000_2024.12.03.626612v1.63","doi-asserted-by":"crossref","unstructured":"Lancaster AK , Single RM , Solberg OD , et al. PyPop update\u2013a software pipeline for large-scale multilocus population genomics. Wiley Online Library 2007.","DOI":"10.1111\/j.1399-0039.2006.00769.x"},{"key":"2024121000212836000_2024.12.03.626612v1.64","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/152.1.393"},{"key":"2024121000212836000_2024.12.03.626612v1.65","doi-asserted-by":"publisher","DOI":"10.1017\/S0016672300032560"},{"key":"2024121000212836000_2024.12.03.626612v1.66","unstructured":"R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing. (No Title). 2013."},{"issue":"D1","key":"2024121000212836000_2024.12.03.626612v1.67","first-page":"D423","article-title":"The IPD and IMGT\/HLA database: allele variant databases","volume":"43","year":"2014","journal-title":"Nucleic Acids Research"},{"key":"2024121000212836000_2024.12.03.626612v1.68","doi-asserted-by":"publisher","DOI":"10.3343\/alm.2017.37.1.45"},{"key":"2024121000212836000_2024.12.03.626612v1.69","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.2.605"},{"issue":"2","key":"2024121000212836000_2024.12.03.626612v1.70","first-page":"435","article-title":"The reactivity of Bw4+ HLA-B and HLA-A alleles with KIR3DL1: implications for patient and donor suitability for haploidentical stem cell transplantations. Blood","volume":"112","year":"2008","journal-title":"The Journal of the American Society of Hematology"},{"key":"2024121000212836000_2024.12.03.626612v1.71","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501358"},{"key":"2024121000212836000_2024.12.03.626612v1.72","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091010"},{"key":"2024121000212836000_2024.12.03.626612v1.73","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200425089"},{"key":"2024121000212836000_2024.12.03.626612v1.74","doi-asserted-by":"publisher","DOI":"10.1007\/s00251-017-1000-z"},{"key":"2024121000212836000_2024.12.03.626612v1.75","doi-asserted-by":"publisher","DOI":"10.1038\/ng2111"},{"key":"2024121000212836000_2024.12.03.626612v1.76","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1502469"},{"key":"2024121000212836000_2024.12.03.626612v1.77","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01124"},{"key":"2024121000212836000_2024.12.03.626612v1.78","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.113.149781"},{"key":"2024121000212836000_2024.12.03.626612v1.79","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.16322"},{"key":"2024121000212836000_2024.12.03.626612v1.80","doi-asserted-by":"publisher","DOI":"10.1002\/art.39515"},{"key":"2024121000212836000_2024.12.03.626612v1.81","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu051"},{"key":"2024121000212836000_2024.12.03.626612v1.82","doi-asserted-by":"publisher","DOI":"10.1159\/000019138"},{"key":"2024121000212836000_2024.12.03.626612v1.83","doi-asserted-by":"publisher","DOI":"10.1111\/j.0001-2815.2004.00192.x"},{"key":"2024121000212836000_2024.12.03.626612v1.84","doi-asserted-by":"publisher","DOI":"10.1038\/ng2077"},{"key":"2024121000212836000_2024.12.03.626612v1.85","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiq075"},{"key":"2024121000212836000_2024.12.03.626612v1.86","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0099353"},{"key":"2024121000212836000_2024.12.03.626612v1.87","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2006.12.007"},{"key":"2024121000212836000_2024.12.03.626612v1.88","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001208"},{"key":"2024121000212836000_2024.12.03.626612v1.89","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2540.2001.00895.x"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.12.03.626612","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T07:36:15Z","timestamp":1768462575000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.12.03.626612"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,7]]},"references-count":89,"URL":"https:\/\/doi.org\/10.1101\/2024.12.03.626612","relation":{},"subject":[],"published":{"date-parts":[[2024,12,7]]},"subtype":"preprint"}}