Novel alleles at the lymphotoxin alpha (LTα) locus mark extended HLA haplotypes in native Africans
Identifieur interne : 002A42 ( Istex/Corpus ); précédent : 002A41; suivant : 002A43Novel alleles at the lymphotoxin alpha (LTα) locus mark extended HLA haplotypes in native Africans
Auteurs : Jianming Tang ; Angela D. Myracle ; Susan Allen ; Etienne Karita ; Rosemary Musonda ; Patricia N. Fultz ; Richard A. KaslowSource :
- Human Immunology [ 0198-8859 ] ; 2001.
English descriptors
- KwdEn :
- AIDS, Africans, Allele, Antigen processing, Carrington, Caucasian, Chimpanzee, Cohort, Disease progression, Disequilibrium, Exon, First intron, Genbank sequence, Genotype, Genotyping, HIV-1, HLA, Haplotype, Heterozygosity, Histocompatibility, Homozygosity, Immunol, Kaslow, LTα, Linkage disequilibrium, Locus, MHC, Major histocompatibility, Microsatellite, Native africans, Necrosis, Novel tnfc alleles, OR, Odds ratio, Other hand, PCR, Polymorphism, Proc natl acad, Promoter, Recombination, Rwandan, SNPs, SSCP, SSP, STR, Seronegative, Seropositive, TAP1, TAP2, TNF, TNFc, Tap1, Tap2, Tissue antigens, Tnfc, Tnfc alleles, Tnfc microsatellite, Tnfc variants, Tumor necrosis factor, Vaccine trial, Variant, Zambian, bp, nt, polymorphism.
- Teeft :
- Allele, Antigen processing, Carrington, Caucasian, Chimpanzee, Cohort, Disease progression, Disequilibrium, Exon, First intron, Genbank sequence, Genotype, Genotyping, Haplotype, Heterozygosity, Histocompatibility, Homozygosity, Immunol, Kaslow, Linkage disequilibrium, Locus, Major histocompatibility, Microsatellite, Native africans, Necrosis, Novel tnfc alleles, Odds ratio, Other hand, Polymorphism, Proc natl acad, Promoter, Recombination, Rwandan, Seronegative, Seropositive, Tap1, Tap2, Tissue antigens, Tnfc, Tnfc alleles, Tnfc microsatellite, Tnfc variants, Tumor necrosis factor, Vaccine trial, Variant, Zambian.
Abstract
Abstract: Genetic variations at the closely related tumor necrosis factor alpha (TNFα or TNF) and lymphotoxin alpha (LTα, formerly TNFβ) loci have been well documented in various human populations, and several haplotypes spanning the MHC class I and class II loci are known to carry specific TNF alleles. Genotyping of the TNFc microsatellite within the first intron of LTα in 285 Rwandans and 319 Zambians revealed two predominant alleles, c1 at frequencies of 0.598 and 0.683 and c2 at 0.384 and 0.307, respectively. Overall, the distribution of TNFc genotypes containing the major alleles conformed well to the Hardy-Weinberg equilibrium in both cohorts. Two previously unrecognized minor TNFc alleles were also detected: the first, designated c0, was found in 10 native Africans and was the only allele present in 10 chimpanzees; the second, designated c3, was seen in 6 other African patients. Further genotyping at loci for HLA class I, class II, and for transporters associated with antigen processing, subunit 1 (TAP1) in those 16 individuals suggested a tight, stable extended haplotype involving c0 and 26Asn (LTα)-TNF3 (TNF promoter −238A and −308G)-DRB1∗1503-DQB1∗0602-TAP1.2 (333Val)-TAP1.4 (637Gly). The c3 allele was observed on another extended haplotype with 26Thr (LTα)-TNF1 (TNF promoter −238G and −308G)-DQB1∗0102-DQB1∗0501-TAP1∗0101 (333Ile and 637Asp). The c3-tagged haplotype further extended to Cw∗15 at the HLA class I C locus, but no specific A or B alleles could be unambiguously assigned. Positive associations between c2 homozygosity and HIV-1 seronegative status in both Rwandans and Zambians (odds ratio = 2.03 and 2.00, p = 0.04 and 0.07, respectively) had little effect on the haplotype assignments. These findings suggest a preferential expansion of the human TNFc dinucleotide (CT/AG) repeat sequence and further imply the existence of two extended MHC lineages that have not been disrupted by recombinations.
Url:
DOI: 10.1016/S0198-8859(00)00252-4
Links to Exploration step
ISTEX:81FF407AFFC3116961D421CC3332F95D850AF3C7Le document en format XML
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Myracle</name><affiliation><mods:affiliation>Program in Epidemiology of Infection and Immunity (J.T., A.D.M., R.A.K.), School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA</mods:affiliation></affiliation></author><author><name sortKey="Allen, Susan" sort="Allen, Susan" uniqKey="Allen S" first="Susan" last="Allen">Susan Allen</name><affiliation><mods:affiliation>Department of Epidemiology and International Health (A.D.M., S.A., R.A.K.), University of Alabama at Birmingham, Birmingham, AL, USA</mods:affiliation></affiliation></author><author><name sortKey="Karita, Etienne" sort="Karita, Etienne" uniqKey="Karita E" first="Etienne" last="Karita">Etienne Karita</name><affiliation><mods:affiliation>National AIDS Control Program (E.K.), Kigali, Rwanda</mods:affiliation></affiliation></author><author><name sortKey="Musonda, Rosemary" sort="Musonda, Rosemary" uniqKey="Musonda R" first="Rosemary" last="Musonda">Rosemary Musonda</name><affiliation><mods:affiliation>Tropical Disease Research Center (R.M.), Ndona, Zambia</mods:affiliation></affiliation></author><author><name sortKey="Fultz, Patricia N" sort="Fultz, Patricia N" uniqKey="Fultz P" first="Patricia N" last="Fultz">Patricia N. Fultz</name><affiliation><mods:affiliation>Department of Microbiology (P.N.F.), University of Alabama at Birmingham, Birmingham, AL, USA</mods:affiliation></affiliation></author><author><name sortKey="Kaslow, Richard A" sort="Kaslow, Richard A" uniqKey="Kaslow R" first="Richard A" last="Kaslow">Richard A. Kaslow</name><affiliation><mods:affiliation>Program in Epidemiology of Infection and Immunity (J.T., A.D.M., R.A.K.), School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Immunology</title><title level="j" type="abbrev">HIM</title><idno type="ISSN">0198-8859</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2001">2001</date><biblScope unit="volume">62</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="269">269</biblScope><biblScope unit="page" to="278">278</biblScope></imprint><idno type="ISSN">0198-8859</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0198-8859</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>AIDS</term><term>Africans</term><term>Allele</term><term>Antigen processing</term><term>Carrington</term><term>Caucasian</term><term>Chimpanzee</term><term>Cohort</term><term>Disease progression</term><term>Disequilibrium</term><term>Exon</term><term>First intron</term><term>Genbank sequence</term><term>Genotype</term><term>Genotyping</term><term>HIV-1</term><term>HLA</term><term>Haplotype</term><term>Heterozygosity</term><term>Histocompatibility</term><term>Homozygosity</term><term>Immunol</term><term>Kaslow</term><term>LTα</term><term>Linkage disequilibrium</term><term>Locus</term><term>MHC</term><term>Major histocompatibility</term><term>Microsatellite</term><term>Native africans</term><term>Necrosis</term><term>Novel tnfc alleles</term><term>OR</term><term>Odds ratio</term><term>Other hand</term><term>PCR</term><term>Polymorphism</term><term>Proc natl acad</term><term>Promoter</term><term>Recombination</term><term>Rwandan</term><term>SNPs</term><term>SSCP</term><term>SSP</term><term>STR</term><term>Seronegative</term><term>Seropositive</term><term>TAP1</term><term>TAP2</term><term>TNF</term><term>TNFc</term><term>Tap1</term><term>Tap2</term><term>Tissue antigens</term><term>Tnfc</term><term>Tnfc alleles</term><term>Tnfc microsatellite</term><term>Tnfc variants</term><term>Tumor necrosis factor</term><term>Vaccine trial</term><term>Variant</term><term>Zambian</term><term>bp</term><term>nt</term><term>polymorphism</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Allele</term><term>Antigen processing</term><term>Carrington</term><term>Caucasian</term><term>Chimpanzee</term><term>Cohort</term><term>Disease progression</term><term>Disequilibrium</term><term>Exon</term><term>First intron</term><term>Genbank sequence</term><term>Genotype</term><term>Genotyping</term><term>Haplotype</term><term>Heterozygosity</term><term>Histocompatibility</term><term>Homozygosity</term><term>Immunol</term><term>Kaslow</term><term>Linkage disequilibrium</term><term>Locus</term><term>Major histocompatibility</term><term>Microsatellite</term><term>Native africans</term><term>Necrosis</term><term>Novel tnfc alleles</term><term>Odds ratio</term><term>Other hand</term><term>Polymorphism</term><term>Proc natl acad</term><term>Promoter</term><term>Recombination</term><term>Rwandan</term><term>Seronegative</term><term>Seropositive</term><term>Tap1</term><term>Tap2</term><term>Tissue antigens</term><term>Tnfc</term><term>Tnfc alleles</term><term>Tnfc microsatellite</term><term>Tnfc variants</term><term>Tumor necrosis factor</term><term>Vaccine trial</term><term>Variant</term><term>Zambian</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Genetic variations at the closely related tumor necrosis factor alpha (TNFα or TNF) and lymphotoxin alpha (LTα, formerly TNFβ) loci have been well documented in various human populations, and several haplotypes spanning the MHC class I and class II loci are known to carry specific TNF alleles. Genotyping of the TNFc microsatellite within the first intron of LTα in 285 Rwandans and 319 Zambians revealed two predominant alleles, c1 at frequencies of 0.598 and 0.683 and c2 at 0.384 and 0.307, respectively. Overall, the distribution of TNFc genotypes containing the major alleles conformed well to the Hardy-Weinberg equilibrium in both cohorts. Two previously unrecognized minor TNFc alleles were also detected: the first, designated c0, was found in 10 native Africans and was the only allele present in 10 chimpanzees; the second, designated c3, was seen in 6 other African patients. Further genotyping at loci for HLA class I, class II, and for transporters associated with antigen processing, subunit 1 (TAP1) in those 16 individuals suggested a tight, stable extended haplotype involving c0 and 26Asn (LTα)-TNF3 (TNF promoter −238A and −308G)-DRB1∗1503-DQB1∗0602-TAP1.2 (333Val)-TAP1.4 (637Gly). The c3 allele was observed on another extended haplotype with 26Thr (LTα)-TNF1 (TNF promoter −238G and −308G)-DQB1∗0102-DQB1∗0501-TAP1∗0101 (333Ile and 637Asp). The c3-tagged haplotype further extended to Cw∗15 at the HLA class I C locus, but no specific A or B alleles could be unambiguously assigned. Positive associations between c2 homozygosity and HIV-1 seronegative status in both Rwandans and Zambians (odds ratio = 2.03 and 2.00, p = 0.04 and 0.07, respectively) had little effect on the haplotype assignments. These findings suggest a preferential expansion of the human TNFc dinucleotide (CT/AG) repeat sequence and further imply the existence of two extended MHC lineages that have not been disrupted by recombinations.</div></front></TEI><istex><corpusName>elsevier</corpusName><keywords><teeft><json:string>allele</json:string><json:string>haplotype</json:string><json:string>tnfc</json:string><json:string>polymorphism</json:string><json:string>rwandan</json:string><json:string>zambian</json:string><json:string>immunol</json:string><json:string>exon</json:string><json:string>chimpanzee</json:string><json:string>tap1</json:string><json:string>genotype</json:string><json:string>microsatellite</json:string><json:string>recombination</json:string><json:string>genotyping</json:string><json:string>seronegative</json:string><json:string>promoter</json:string><json:string>tumor necrosis factor</json:string><json:string>histocompatibility</json:string><json:string>heterozygosity</json:string><json:string>kaslow</json:string><json:string>homozygosity</json:string><json:string>novel tnfc alleles</json:string><json:string>tap2</json:string><json:string>carrington</json:string><json:string>seropositive</json:string><json:string>cohort</json:string><json:string>disequilibrium</json:string><json:string>tnfc alleles</json:string><json:string>tissue antigens</json:string><json:string>proc natl acad</json:string><json:string>tnfc microsatellite</json:string><json:string>locus</json:string><json:string>caucasian</json:string><json:string>antigen processing</json:string><json:string>tnfc variants</json:string><json:string>linkage disequilibrium</json:string><json:string>major histocompatibility</json:string><json:string>disease progression</json:string><json:string>first intron</json:string><json:string>vaccine trial</json:string><json:string>genbank sequence</json:string><json:string>other hand</json:string><json:string>native africans</json:string><json:string>odds ratio</json:string><json:string>necrosis</json:string><json:string>variant</json:string></teeft></keywords><author><json:item><name>Jianming Tang</name><affiliations><json:string>E-mail: jtang@uab.edu</json:string><json:string>Program in Epidemiology of Infection and Immunity (J.T., A.D.M., R.A.K.), School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA</json:string></affiliations></json:item><json:item><name>Angela D Myracle</name><affiliations><json:string>Program in Epidemiology of Infection and Immunity (J.T., A.D.M., R.A.K.), School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA</json:string></affiliations></json:item><json:item><name>Susan Allen</name><affiliations><json:string>Department of Epidemiology and International Health (A.D.M., S.A., R.A.K.), University of Alabama at Birmingham, Birmingham, AL, USA</json:string></affiliations></json:item><json:item><name>Etienne Karita</name><affiliations><json:string>National AIDS Control Program (E.K.), Kigali, Rwanda</json:string></affiliations></json:item><json:item><name>Rosemary Musonda</name><affiliations><json:string>Tropical Disease Research Center (R.M.), Ndona, Zambia</json:string></affiliations></json:item><json:item><name>Patricia N Fultz</name><affiliations><json:string>Department of Microbiology (P.N.F.), University of Alabama at Birmingham, Birmingham, AL, USA</json:string></affiliations></json:item><json:item><name>Richard A Kaslow</name><affiliations><json:string>Program in Epidemiology of Infection and Immunity (J.T., A.D.M., R.A.K.), School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Africans</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>HLA</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>polymorphism</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>LTα</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>TNFc</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>AIDS : acquired immune deficiency syndrome</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>bp : base pairs</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>HIV-1 : human immunodeficiency virus type 1</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>HLA : human leukocyte antigen</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>LTα : lymphotoxin alpha</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MHC : major histocompatibility complex</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>nt : nucleotides</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>OR : odds ratio</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PCR : polymerase chain reaction</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>SNPs : single nucleotide polymorphisms</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>SSCP : single-strand conformation polymorphism</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>SSP : sequence-specific primers</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>STR : short tandem repeat (DNA sequences)</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>TAP1 : transporter associated with antigen processing, subunit 1</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>TAP2 : transporter associated with antigen processing, subunit 2</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>TNF : tumor necrosis factor</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>TNFc : TNFc microsatellite</value></json:item></subject><language><json:string>eng</json:string></language><originalGenre><json:string>Full-length article</json:string></originalGenre><abstract>Genetic variations at the closely related tumor necrosis factor alpha (TNFα or TNF) and lymphotoxin alpha (LTα, formerly TNFβ) loci have been well documented in various human populations, and several haplotypes spanning the MHC class I and class II loci are known to carry specific TNF alleles. Genotyping of the TNFc microsatellite within the first intron of LTα in 285 Rwandans and 319 Zambians revealed two predominant alleles, c1 at frequencies of 0.598 and 0.683 and c2 at 0.384 and 0.307, respectively. Overall, the distribution of TNFc genotypes containing the major alleles conformed well to the Hardy-Weinberg equilibrium in both cohorts. Two previously unrecognized minor TNFc alleles were also detected: the first, designated c0, was found in 10 native Africans and was the only allele present in 10 chimpanzees; the second, designated c3, was seen in 6 other African patients. Further genotyping at loci for HLA class I, class II, and for transporters associated with antigen processing, subunit 1 (TAP1) in those 16 individuals suggested a tight, stable extended haplotype involving c0 and 26Asn (LTα)-TNF3 (TNF promoter −238A and −308G)-DRB1∗1503-DQB1∗0602-TAP1.2 (333Val)-TAP1.4 (637Gly). The c3 allele was observed on another extended haplotype with 26Thr (LTα)-TNF1 (TNF promoter −238G and −308G)-DQB1∗0102-DQB1∗0501-TAP1∗0101 (333Ile and 637Asp). The c3-tagged haplotype further extended to Cw∗15 at the HLA class I C locus, but no specific A or B alleles could be unambiguously assigned. Positive associations between c2 homozygosity and HIV-1 seronegative status in both Rwandans and Zambians (odds ratio = 2.03 and 2.00, p = 0.04 and 0.07, respectively) had little effect on the haplotype assignments. These findings suggest a preferential expansion of the human TNFc dinucleotide (CT/AG) repeat sequence and further imply the existence of two extended MHC lineages that have not been disrupted by recombinations.</abstract><qualityIndicators><score>8</score><pdfVersion>1.2</pdfVersion><pdfPageSize>596 x 792 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>22</keywordCount><abstractCharCount>1934</abstractCharCount><pdfWordCount>5452</pdfWordCount><pdfCharCount>34637</pdfCharCount><pdfPageCount>10</pdfPageCount><abstractWordCount>291</abstractWordCount></qualityIndicators><title>Novel alleles at the lymphotoxin alpha (LTα) locus mark extended HLA haplotypes in native Africans</title><pii><json:string>S0198-8859(00)00252-4</json:string></pii><genre><json:string>research-article</json:string></genre><host><title>Human Immunology</title><language><json:string>unknown</json:string></language><publicationDate>2001</publicationDate><issn><json:string>0198-8859</json:string></issn><pii><json:string>S0198-8859(00)X0074-2</json:string></pii><volume>62</volume><issue>3</issue><pages><first>269</first><last>278</last></pages><genre><json:string>journal</json:string></genre></host><categories><wos><json:string>science</json:string><json:string>immunology</json:string></wos><scienceMetrix><json:string>health sciences</json:string><json:string>clinical medicine</json:string><json:string>immunology</json:string></scienceMetrix><inist><json:string>sciences appliquees, technologies et medecines</json:string><json:string>sciences biologiques et medicales</json:string><json:string>sciences medicales</json:string><json:string>dermatologie</json:string></inist></categories><publicationDate>2001</publicationDate><copyrightDate>2001</copyrightDate><doi><json:string>10.1016/S0198-8859(00)00252-4</json:string></doi><id>81FF407AFFC3116961D421CC3332F95D850AF3C7</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/81FF407AFFC3116961D421CC3332F95D850AF3C7/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/81FF407AFFC3116961D421CC3332F95D850AF3C7/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/81FF407AFFC3116961D421CC3332F95D850AF3C7/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Novel alleles at the lymphotoxin alpha (LTα) locus mark extended HLA haplotypes in native Africans</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>ELSEVIER</publisher><availability><p>©2001 American Society for Histocompatibility and Immunogenetics</p></availability><date>2001</date></publicationStmt><notesStmt><note type="content">FIGURE 1: Automated separation and detection of TNFc microsatellite alleles amplified by PCR. The allelic products were labeled with Cy5, denatured, and separated through 6% PAGE-plus (Amresco, Solon, OH, USA) gel prepared in 1× TBE buffer (90 mM Tris-boric acid, pH 8.3, 2 mM EDTA) and 6 M urea. The marker DNA ranging from 85 nt to 115 nt is shown. Arrow and arrowhead indicate alleles c0 (91-nt, with 12 CT/AG repeats) and c3 (97-nt, with 15 CT/AG repeats), respectively. The most common TNFc alleles are c1 (93-nt, with 13 CT/AG repeats) and c2 (95-nt, with 14 CT/AG repeats).</note><note type="content">FIGURE 2: HLA profile in Rwandans (RWA) and Zambians (ZMB) carrying novel TNFc alleles. The MHC and related loci being typed are drawn to approximate scale [60]. Curved double arrows separate the evolutionarily conserved HLA blocks between which recombination often occur to generate new haplotypes [47]. Two additional recombination hot spots (indicated by arrows) are fine mapped to HLA-B [52] and TAP2 [49]. For homozygous genotypes the alleles are only listed once. Genetic variants that form stable haplotypes despite the recombination hot spots are either underlined or highlighted in bold. Partial data from 10 chimpanzees show only a single haplotype sequence. In addition, the TNFa-308G/G homozygous genotype (not shown) is found in all 16 Africans as well as 10 chimpanzees.</note><note type="content">TABLE 1: Oligonucleotides used to amplify polymorphic CD4 STR, TNFc microsatellite, and TAP1 coding sequences</note><note type="content">TABLE 2: CD4 STR allele frequencies observed in Rwandans and Zambians</note><note type="content">TABLE 3: Frequencies of TNFc alleles and genotypes observed in Rwandans, Zambians, and compared with Caucasians</note><note type="content">TABLE 4: Comparison of TNFc variants among HIV-1+ and HIV-1− groups from Rwanda and Zambia</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Novel alleles at the lymphotoxin alpha (LTα) locus mark extended HLA haplotypes in native Africans</title><author xml:id="author-0000"><persName><forename type="first">Jianming</forename><surname>Tang</surname></persName><email>jtang@uab.edu</email><note type="biography">Address reprint requests to: Dr. Jianming Tang, Division of Geographic Medicine, BBRB Box 7, 1530 3rd Ave South, University of Alabama at Birmingham, Birmingham, AL 39294; Tel: (205) 975 8608; Fax: (205) 934 8665</note><affiliation>Address reprint requests to: Dr. Jianming Tang, Division of Geographic Medicine, BBRB Box 7, 1530 3rd Ave South, University of Alabama at Birmingham, Birmingham, AL 39294; Tel: (205) 975 8608; Fax: (205) 934 8665</affiliation><affiliation>Program in Epidemiology of Infection and Immunity (J.T., A.D.M., R.A.K.), School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Angela D</forename><surname>Myracle</surname></persName><affiliation>Program in Epidemiology of Infection and Immunity (J.T., A.D.M., R.A.K.), School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA</affiliation></author><author xml:id="author-0002"><persName><forename type="first">Susan</forename><surname>Allen</surname></persName><affiliation>Department of Epidemiology and International Health (A.D.M., S.A., R.A.K.), University of Alabama at Birmingham, Birmingham, AL, USA</affiliation></author><author xml:id="author-0003"><persName><forename type="first">Etienne</forename><surname>Karita</surname></persName><affiliation>National AIDS Control Program (E.K.), Kigali, Rwanda</affiliation></author><author xml:id="author-0004"><persName><forename type="first">Rosemary</forename><surname>Musonda</surname></persName><affiliation>Tropical Disease Research Center (R.M.), Ndona, Zambia</affiliation></author><author xml:id="author-0005"><persName><forename type="first">Patricia N</forename><surname>Fultz</surname></persName><affiliation>Department of Microbiology (P.N.F.), University of Alabama at Birmingham, Birmingham, AL, USA</affiliation></author><author xml:id="author-0006"><persName><forename type="first">Richard A</forename><surname>Kaslow</surname></persName><affiliation>Program in Epidemiology of Infection and Immunity (J.T., A.D.M., R.A.K.), School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA</affiliation></author><idno type="istex">81FF407AFFC3116961D421CC3332F95D850AF3C7</idno><idno type="DOI">10.1016/S0198-8859(00)00252-4</idno><idno type="PII">S0198-8859(00)00252-4</idno></analytic><monogr><title level="j">Human Immunology</title><title level="j" type="abbrev">HIM</title><idno type="pISSN">0198-8859</idno><idno type="PII">S0198-8859(00)X0074-2</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2001"></date><biblScope unit="volume">62</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="269">269</biblScope><biblScope unit="page" to="278">278</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2001</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Genetic variations at the closely related tumor necrosis factor alpha (TNFα or TNF) and lymphotoxin alpha (LTα, formerly TNFβ) loci have been well documented in various human populations, and several haplotypes spanning the MHC class I and class II loci are known to carry specific TNF alleles. Genotyping of the TNFc microsatellite within the first intron of LTα in 285 Rwandans and 319 Zambians revealed two predominant alleles, c1 at frequencies of 0.598 and 0.683 and c2 at 0.384 and 0.307, respectively. Overall, the distribution of TNFc genotypes containing the major alleles conformed well to the Hardy-Weinberg equilibrium in both cohorts. Two previously unrecognized minor TNFc alleles were also detected: the first, designated c0, was found in 10 native Africans and was the only allele present in 10 chimpanzees; the second, designated c3, was seen in 6 other African patients. Further genotyping at loci for HLA class I, class II, and for transporters associated with antigen processing, subunit 1 (TAP1) in those 16 individuals suggested a tight, stable extended haplotype involving c0 and 26Asn (LTα)-TNF3 (TNF promoter −238A and −308G)-DRB1∗1503-DQB1∗0602-TAP1.2 (333Val)-TAP1.4 (637Gly). The c3 allele was observed on another extended haplotype with 26Thr (LTα)-TNF1 (TNF promoter −238G and −308G)-DQB1∗0102-DQB1∗0501-TAP1∗0101 (333Ile and 637Asp). The c3-tagged haplotype further extended to Cw∗15 at the HLA class I C locus, but no specific A or B alleles could be unambiguously assigned. Positive associations between c2 homozygosity and HIV-1 seronegative status in both Rwandans and Zambians (odds ratio = 2.03 and 2.00, p = 0.04 and 0.07, respectively) had little effect on the haplotype assignments. These findings suggest a preferential expansion of the human TNFc dinucleotide (CT/AG) repeat sequence and further imply the existence of two extended MHC lineages that have not been disrupted by recombinations.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Africans</term></item><item><term>HLA</term></item><item><term>polymorphism</term></item><item><term>LTα</term></item><item><term>TNFc</term></item></list></keywords></textClass><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Abbreviations</head><item><term>AIDS</term><term>acquired immune deficiency syndrome</term></item><item><term>bp</term><term>base pairs</term></item><item><term>HIV-1</term><term>human immunodeficiency virus type 1</term></item><item><term>HLA</term><term>human leukocyte antigen</term></item><item><term>LTα</term><term>lymphotoxin alpha</term></item><item><term>MHC</term><term>major histocompatibility complex</term></item><item><term>nt</term><term>nucleotides</term></item><item><term>OR</term><term>odds ratio</term></item><item><term>PCR</term><term>polymerase chain reaction</term></item><item><term>SNPs</term><term>single nucleotide polymorphisms</term></item><item><term>SSCP</term><term>single-strand conformation polymorphism</term></item><item><term>SSP</term><term>sequence-specific primers</term></item><item><term>STR</term><term>short tandem repeat (DNA sequences)</term></item><item><term>TAP1</term><term>transporter associated with antigen processing, subunit 1</term></item><item><term>TAP2</term><term>transporter associated with antigen processing, subunit 2</term></item><item><term>TNF</term><term>tumor necrosis factor</term></item><item><term>TNFc</term><term>TNFc microsatellite</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2000-11-27">Modified</change><change when="2001">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/81FF407AFFC3116961D421CC3332F95D850AF3C7/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: ce:floats; body; tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"><istex:entity SYSTEM="fx0681" NDATA="IMAGE" name="FX0681"></istex:entity><istex:entity SYSTEM="fx0736" NDATA="IMAGE" name="FX0736"></istex:entity><istex:entity SYSTEM="gr1" NDATA="IMAGE" name="GR1"></istex:entity><istex:entity SYSTEM="gr2" NDATA="IMAGE" name="GR2"></istex:entity></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla" xml:lang="en"><item-info><jid>HIM</jid><aid>5696</aid><ce:pii>S0198-8859(00)00252-4</ce:pii><ce:doi>10.1016/S0198-8859(00)00252-4</ce:doi><ce:copyright type="society" year="2001">American Society for Histocompatibility and Immunogenetics</ce:copyright></item-info><head><ce:title>Novel alleles at the lymphotoxin alpha (LTα) locus mark extended HLA haplotypes in native Africans</ce:title><ce:author-group><ce:author><ce:given-name>Jianming</ce:given-name><ce:surname>Tang</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF2"><ce:sup>b</ce:sup></ce:cross-ref><ce:cross-ref refid="CORR1">*</ce:cross-ref><ce:e-address>jtang@uab.edu</ce:e-address></ce:author><ce:author><ce:given-name>Angela D</ce:given-name><ce:surname>Myracle</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF3"><ce:sup>c</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Susan</ce:given-name><ce:surname>Allen</ce:surname><ce:cross-ref refid="AFF3"><ce:sup>c</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Etienne</ce:given-name><ce:surname>Karita</ce:surname><ce:cross-ref refid="AFF4"><ce:sup>e</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Rosemary</ce:given-name><ce:surname>Musonda</ce:surname><ce:cross-ref refid="AFF5"><ce:sup>f</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Patricia N</ce:given-name><ce:surname>Fultz</ce:surname><ce:cross-ref refid="AFF6"><ce:sup>d</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Richard A</ce:given-name><ce:surname>Kaslow</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF3"><ce:sup>c</ce:sup></ce:cross-ref></ce:author><ce:affiliation id="AFF1"><ce:label>a</ce:label><ce:textfn>Program in Epidemiology of Infection and Immunity (J.T., A.D.M., R.A.K.), School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA</ce:textfn></ce:affiliation><ce:affiliation id="AFF2"><ce:label>b</ce:label><ce:textfn>Division of Geographic Medicine (J.T.), Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA</ce:textfn></ce:affiliation><ce:affiliation id="AFF3"><ce:label>c</ce:label><ce:textfn>Department of Epidemiology and International Health (A.D.M., S.A., R.A.K.), University of Alabama at Birmingham, Birmingham, AL, USA</ce:textfn></ce:affiliation><ce:affiliation id="AFF6"><ce:label>d</ce:label><ce:textfn>Department of Microbiology (P.N.F.), University of Alabama at Birmingham, Birmingham, AL, USA</ce:textfn></ce:affiliation><ce:affiliation id="AFF4"><ce:label>e</ce:label><ce:textfn>National AIDS Control Program (E.K.), Kigali, Rwanda</ce:textfn></ce:affiliation><ce:affiliation id="AFF5"><ce:label>f</ce:label><ce:textfn>Tropical Disease Research Center (R.M.), Ndona, Zambia</ce:textfn></ce:affiliation><ce:correspondence id="CORR1"><ce:label>*</ce:label><ce:text>Address reprint requests to: Dr. Jianming Tang, Division of Geographic Medicine, BBRB Box 7, 1530 3rd Ave South, University of Alabama at Birmingham, Birmingham, AL 39294; Tel: (205) 975 8608; Fax: (205) 934 8665</ce:text></ce:correspondence></ce:author-group><ce:date-received day="27" month="6" year="2000"></ce:date-received><ce:date-revised day="27" month="11" year="2000"></ce:date-revised><ce:date-accepted day="30" month="11" year="2000"></ce:date-accepted><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>Genetic variations at the closely related tumor necrosis factor alpha (TNFα or TNF) and lymphotoxin alpha (LTα, formerly TNFβ) loci have been well documented in various human populations, and several haplotypes spanning the MHC class I and class II loci are known to carry specific TNF alleles. Genotyping of the TNFc microsatellite within the first intron of LTα in 285 Rwandans and 319 Zambians revealed two predominant alleles, c1 at frequencies of 0.598 and 0.683 and c2 at 0.384 and 0.307, respectively. Overall, the distribution of TNFc genotypes containing the major alleles conformed well to the Hardy-Weinberg equilibrium in both cohorts. Two previously unrecognized minor TNFc alleles were also detected: the first, designated c0, was found in 10 native Africans and was the only allele present in 10 chimpanzees; the second, designated c3, was seen in 6 other African patients. Further genotyping at loci for HLA class I, class II, and for transporters associated with antigen processing, subunit 1 (TAP1) in those 16 individuals suggested a tight, stable extended haplotype involving c0 and 26Asn (LTα)-TNF3 (TNF promoter −238A and −308G)-DRB1∗1503-DQB1∗0602-TAP1.2 (333Val)-TAP1.4 (637Gly). The c3 allele was observed on another extended haplotype with 26Thr (LTα)-TNF1 (TNF promoter −238G and −308G)-DQB1∗0102-DQB1∗0501-TAP1∗0101 (333Ile and 637Asp). The c3-tagged haplotype further extended to Cw∗15 at the HLA class I C locus, but no specific A or B alleles could be unambiguously assigned. Positive associations between c2 homozygosity and HIV-1 seronegative status in both Rwandans and Zambians (odds ratio = 2.03 and 2.00, <ce:italic>p</ce:italic> = 0.04 and 0.07, respectively) had little effect on the haplotype assignments. These findings suggest a preferential expansion of the human TNFc dinucleotide (CT/AG) repeat sequence and further imply the existence of two extended MHC lineages that have not been disrupted by recombinations.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords class="keyword"><ce:section-title>Keywords</ce:section-title><ce:keyword><ce:text>Africans</ce:text></ce:keyword><ce:keyword><ce:text>HLA</ce:text></ce:keyword><ce:keyword><ce:text>polymorphism</ce:text></ce:keyword><ce:keyword><ce:text>LTα</ce:text></ce:keyword><ce:keyword><ce:text>TNFc</ce:text></ce:keyword></ce:keywords><ce:keywords class="abr"><ce:section-title>Abbreviations</ce:section-title><ce:keyword><ce:text>AIDS</ce:text><ce:keyword><ce:text>acquired immune deficiency syndrome</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>bp</ce:text><ce:keyword><ce:text>base pairs</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>HIV-1</ce:text><ce:keyword><ce:text>human immunodeficiency virus type 1</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>HLA</ce:text><ce:keyword><ce:text>human leukocyte antigen</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>LTα</ce:text><ce:keyword><ce:text>lymphotoxin alpha</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>MHC</ce:text><ce:keyword><ce:text>major histocompatibility complex</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>nt</ce:text><ce:keyword><ce:text>nucleotides</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>OR</ce:text><ce:keyword><ce:text>odds ratio</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>PCR</ce:text><ce:keyword><ce:text>polymerase chain reaction</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>SNPs</ce:text><ce:keyword><ce:text>single nucleotide polymorphisms</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>SSCP</ce:text><ce:keyword><ce:text>single-strand conformation polymorphism</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>SSP</ce:text><ce:keyword><ce:text>sequence-specific primers</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>STR</ce:text><ce:keyword><ce:text>short tandem repeat (DNA sequences)</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>TAP1</ce:text><ce:keyword><ce:text>transporter associated with antigen processing, subunit 1</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>TAP2</ce:text><ce:keyword><ce:text>transporter associated with antigen processing, subunit 2</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>TNF</ce:text><ce:keyword><ce:text>tumor necrosis factor</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>TNFc</ce:text><ce:keyword><ce:text>TNFc microsatellite</ce:text></ce:keyword></ce:keyword></ce:keywords></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Novel alleles at the lymphotoxin alpha (LTα) locus mark extended HLA haplotypes in native Africans</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Novel alleles at the lymphotoxin alpha (LTα) locus mark extended HLA haplotypes in native Africans</title></titleInfo><name type="personal"><namePart type="given">Jianming</namePart><namePart type="family">Tang</namePart><affiliation>E-mail: jtang@uab.edu</affiliation><affiliation>Program in Epidemiology of Infection and Immunity (J.T., A.D.M., R.A.K.), School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA</affiliation><description>Address reprint requests to: Dr. Jianming Tang, Division of Geographic Medicine, BBRB Box 7, 1530 3rd Ave South, University of Alabama at Birmingham, Birmingham, AL 39294; Tel: (205) 975 8608; Fax: (205) 934 8665</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Angela D</namePart><namePart type="family">Myracle</namePart><affiliation>Program in Epidemiology of Infection and Immunity (J.T., A.D.M., R.A.K.), School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Susan</namePart><namePart type="family">Allen</namePart><affiliation>Department of Epidemiology and International Health (A.D.M., S.A., R.A.K.), University of Alabama at Birmingham, Birmingham, AL, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Etienne</namePart><namePart type="family">Karita</namePart><affiliation>National AIDS Control Program (E.K.), Kigali, Rwanda</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Rosemary</namePart><namePart type="family">Musonda</namePart><affiliation>Tropical Disease Research Center (R.M.), Ndona, Zambia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Patricia N</namePart><namePart type="family">Fultz</namePart><affiliation>Department of Microbiology (P.N.F.), University of Alabama at Birmingham, Birmingham, AL, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Richard A</namePart><namePart type="family">Kaslow</namePart><affiliation>Program in Epidemiology of Infection and Immunity (J.T., A.D.M., R.A.K.), School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">2001</dateIssued><dateModified encoding="w3cdtf">2000-11-27</dateModified><copyrightDate encoding="w3cdtf">2001</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><abstract lang="en">Abstract: Genetic variations at the closely related tumor necrosis factor alpha (TNFα or TNF) and lymphotoxin alpha (LTα, formerly TNFβ) loci have been well documented in various human populations, and several haplotypes spanning the MHC class I and class II loci are known to carry specific TNF alleles. Genotyping of the TNFc microsatellite within the first intron of LTα in 285 Rwandans and 319 Zambians revealed two predominant alleles, c1 at frequencies of 0.598 and 0.683 and c2 at 0.384 and 0.307, respectively. Overall, the distribution of TNFc genotypes containing the major alleles conformed well to the Hardy-Weinberg equilibrium in both cohorts. Two previously unrecognized minor TNFc alleles were also detected: the first, designated c0, was found in 10 native Africans and was the only allele present in 10 chimpanzees; the second, designated c3, was seen in 6 other African patients. Further genotyping at loci for HLA class I, class II, and for transporters associated with antigen processing, subunit 1 (TAP1) in those 16 individuals suggested a tight, stable extended haplotype involving c0 and 26Asn (LTα)-TNF3 (TNF promoter −238A and −308G)-DRB1∗1503-DQB1∗0602-TAP1.2 (333Val)-TAP1.4 (637Gly). The c3 allele was observed on another extended haplotype with 26Thr (LTα)-TNF1 (TNF promoter −238G and −308G)-DQB1∗0102-DQB1∗0501-TAP1∗0101 (333Ile and 637Asp). The c3-tagged haplotype further extended to Cw∗15 at the HLA class I C locus, but no specific A or B alleles could be unambiguously assigned. Positive associations between c2 homozygosity and HIV-1 seronegative status in both Rwandans and Zambians (odds ratio = 2.03 and 2.00, p = 0.04 and 0.07, respectively) had little effect on the haplotype assignments. These findings suggest a preferential expansion of the human TNFc dinucleotide (CT/AG) repeat sequence and further imply the existence of two extended MHC lineages that have not been disrupted by recombinations.</abstract><note type="content">FIGURE 1: Automated separation and detection of TNFc microsatellite alleles amplified by PCR. The allelic products were labeled with Cy5, denatured, and separated through 6% PAGE-plus (Amresco, Solon, OH, USA) gel prepared in 1× TBE buffer (90 mM Tris-boric acid, pH 8.3, 2 mM EDTA) and 6 M urea. The marker DNA ranging from 85 nt to 115 nt is shown. Arrow and arrowhead indicate alleles c0 (91-nt, with 12 CT/AG repeats) and c3 (97-nt, with 15 CT/AG repeats), respectively. The most common TNFc alleles are c1 (93-nt, with 13 CT/AG repeats) and c2 (95-nt, with 14 CT/AG repeats).</note><note type="content">FIGURE 2: HLA profile in Rwandans (RWA) and Zambians (ZMB) carrying novel TNFc alleles. The MHC and related loci being typed are drawn to approximate scale [60]. Curved double arrows separate the evolutionarily conserved HLA blocks between which recombination often occur to generate new haplotypes [47]. Two additional recombination hot spots (indicated by arrows) are fine mapped to HLA-B [52] and TAP2 [49]. For homozygous genotypes the alleles are only listed once. Genetic variants that form stable haplotypes despite the recombination hot spots are either underlined or highlighted in bold. Partial data from 10 chimpanzees show only a single haplotype sequence. In addition, the TNFa-308G/G homozygous genotype (not shown) is found in all 16 Africans as well as 10 chimpanzees.</note><note type="content">TABLE 1: Oligonucleotides used to amplify polymorphic CD4 STR, TNFc microsatellite, and TAP1 coding sequences</note><note type="content">TABLE 2: CD4 STR allele frequencies observed in Rwandans and Zambians</note><note type="content">TABLE 3: Frequencies of TNFc alleles and genotypes observed in Rwandans, Zambians, and compared with Caucasians</note><note type="content">TABLE 4: Comparison of TNFc variants among HIV-1+ and HIV-1− groups from Rwanda and Zambia</note><subject lang="en"><genre>Keywords</genre><topic>Africans</topic><topic>HLA</topic><topic>polymorphism</topic><topic>LTα</topic><topic>TNFc</topic></subject><subject lang="en"><genre>Abbreviations</genre><topic>AIDS : acquired immune deficiency syndrome</topic><topic>bp : base pairs</topic><topic>HIV-1 : human immunodeficiency virus type 1</topic><topic>HLA : human leukocyte antigen</topic><topic>LTα : lymphotoxin alpha</topic><topic>MHC : major histocompatibility complex</topic><topic>nt : nucleotides</topic><topic>OR : odds ratio</topic><topic>PCR : polymerase chain reaction</topic><topic>SNPs : single nucleotide polymorphisms</topic><topic>SSCP : single-strand conformation polymorphism</topic><topic>SSP : sequence-specific primers</topic><topic>STR : short tandem repeat (DNA sequences)</topic><topic>TAP1 : transporter associated with antigen processing, subunit 1</topic><topic>TAP2 : transporter associated with antigen processing, subunit 2</topic><topic>TNF : tumor necrosis factor</topic><topic>TNFc : TNFc microsatellite</topic></subject><relatedItem type="host"><titleInfo><title>Human Immunology</title></titleInfo><titleInfo type="abbreviated"><title>HIM</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">200103</dateIssued></originInfo><identifier type="ISSN">0198-8859</identifier><identifier type="PII">S0198-8859(00)X0074-2</identifier><part><date>200103</date><detail type="volume"><number>62</number><caption>vol.</caption></detail><detail type="issue"><number>3</number><caption>no.</caption></detail><extent unit="issue-pages"><start>201</start><end>298</end></extent><extent unit="pages"><start>269</start><end>278</end></extent></part></relatedItem><identifier type="istex">81FF407AFFC3116961D421CC3332F95D850AF3C7</identifier><identifier type="ark">ark:/67375/6H6-X2J3HVW9-3</identifier><identifier type="DOI">10.1016/S0198-8859(00)00252-4</identifier><identifier type="PII">S0198-8859(00)00252-4</identifier><accessCondition type="use and reproduction" contentType="copyright">©2001 American Society for Histocompatibility and Immunogenetics</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</recordContentSource><recordOrigin>American Society for Histocompatibility and Immunogenetics, ©2001</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/document/81FF407AFFC3116961D421CC3332F95D850AF3C7/metadata/json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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