Complex haplotypic structure of the central MHC region flanking TNF in a West African population
TNF polymorphisms have been associated with susceptibility to malaria and other infectious and inflammatory conditions. We investigated a sample of 150 West African chromosomes to determine linkage disequilibrium (LD) between 25 SNP markers located in an 80 kb segment of the MHC Class III region enc...
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| Veröffentlicht in: | Genes and immunity 2003-10, Vol.4 (7), p.476-486 |
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| creator | Ackerman, H C Ribas, G Jallow, M Mott, R Neville, M Sisay-Joof, F Pinder, M Campbell, R D Kwiatkowski, D P |
| description | TNF
polymorphisms have been associated with susceptibility to malaria and other infectious and inflammatory conditions. We investigated a sample of 150 West African chromosomes to determine linkage disequilibrium (LD) between 25 SNP markers located in an 80 kb segment of the MHC Class III region encompassing
TNF
and eight neighbouring genes. We observed 45 haplotypes, and 22 of them comprise 80% of the sample. The pattern of LD is remarkably patchy, such that many markers show no LD with adjacent markers but high LD with markers that are much further away. We introduce a method of examining the implications of LD data for disease association studies based on sample size considerations: this shows that certain
TNF
polymorphisms would be likely to yield positive associations if the true disease allele resided in
LTA
or
BAT1
. We conclude that detailed marker maps are needed to resolve the causal origin of disease associations observed at the
TNF
locus. |
| doi_str_mv | 10.1038/sj.gene.6364008 |
| format | Article |
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polymorphisms have been associated with susceptibility to malaria and other infectious and inflammatory conditions. We investigated a sample of 150 West African chromosomes to determine linkage disequilibrium (LD) between 25 SNP markers located in an 80 kb segment of the MHC Class III region encompassing
TNF
and eight neighbouring genes. We observed 45 haplotypes, and 22 of them comprise 80% of the sample. The pattern of LD is remarkably patchy, such that many markers show no LD with adjacent markers but high LD with markers that are much further away. We introduce a method of examining the implications of LD data for disease association studies based on sample size considerations: this shows that certain
TNF
polymorphisms would be likely to yield positive associations if the true disease allele resided in
LTA
or
BAT1
. We conclude that detailed marker maps are needed to resolve the causal origin of disease associations observed at the
TNF
locus.</description><identifier>ISSN: 1466-4879</identifier><identifier>EISSN: 1476-5470</identifier><identifier>DOI: 10.1038/sj.gene.6364008</identifier><identifier>PMID: 14551600</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Adult ; Alleles ; Antigens ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Cytokines ; Disease ; Entropy ; Female ; full-paper ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Gambia ; Gene Expression ; Gene Frequency ; Gene mapping ; Genes ; Genetic aspects ; Genetic Markers ; Genetic Predisposition to Disease ; Genetics, Population ; Genotype ; Haplotypes ; Health aspects ; Histocompatibility antigens (hla, h-2 and other systems) ; Human Genetics ; Humans ; Immune response ; Immunology ; Inflammation ; Linkage Disequilibrium ; Major histocompatibility complex ; Major Histocompatibility Complex - genetics ; Malaria ; Male ; Molecular immunology ; Polymorphism, Single Nucleotide ; Proteins ; Single-nucleotide polymorphism ; Tumor necrosis factor ; Tumor Necrosis Factor-alpha - genetics ; Tumor necrosis factor-TNF</subject><ispartof>Genes and immunity, 2003-10, Vol.4 (7), p.476-486</ispartof><rights>Springer Nature Limited 2003</rights><rights>2004 INIST-CNRS</rights><rights>COPYRIGHT 2003 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Oct 2003</rights><rights>Nature Publishing Group 2003.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c551t-30571ada01837008dabb3e449109fbf69fbb9d0584e6ecf2f59251f94c26d5a13</citedby><cites>FETCH-LOGICAL-c551t-30571ada01837008dabb3e449109fbf69fbb9d0584e6ecf2f59251f94c26d5a13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/sj.gene.6364008$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.gene.6364008$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15210150$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14551600$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ackerman, H C</creatorcontrib><creatorcontrib>Ribas, G</creatorcontrib><creatorcontrib>Jallow, M</creatorcontrib><creatorcontrib>Mott, R</creatorcontrib><creatorcontrib>Neville, M</creatorcontrib><creatorcontrib>Sisay-Joof, F</creatorcontrib><creatorcontrib>Pinder, M</creatorcontrib><creatorcontrib>Campbell, R D</creatorcontrib><creatorcontrib>Kwiatkowski, D P</creatorcontrib><title>Complex haplotypic structure of the central MHC region flanking TNF in a West African population</title><title>Genes and immunity</title><addtitle>Genes Immun</addtitle><addtitle>Genes Immun</addtitle><description>TNF
polymorphisms have been associated with susceptibility to malaria and other infectious and inflammatory conditions. We investigated a sample of 150 West African chromosomes to determine linkage disequilibrium (LD) between 25 SNP markers located in an 80 kb segment of the MHC Class III region encompassing
TNF
and eight neighbouring genes. We observed 45 haplotypes, and 22 of them comprise 80% of the sample. The pattern of LD is remarkably patchy, such that many markers show no LD with adjacent markers but high LD with markers that are much further away. We introduce a method of examining the implications of LD data for disease association studies based on sample size considerations: this shows that certain
TNF
polymorphisms would be likely to yield positive associations if the true disease allele resided in
LTA
or
BAT1
. We conclude that detailed marker maps are needed to resolve the causal origin of disease associations observed at the
TNF
locus.</description><subject>Adult</subject><subject>Alleles</subject><subject>Antigens</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Cytokines</subject><subject>Disease</subject><subject>Entropy</subject><subject>Female</subject><subject>full-paper</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Gambia</subject><subject>Gene Expression</subject><subject>Gene Frequency</subject><subject>Gene mapping</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic Markers</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetics, Population</subject><subject>Genotype</subject><subject>Haplotypes</subject><subject>Health aspects</subject><subject>Histocompatibility antigens (hla, h-2 and other systems)</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immunology</subject><subject>Inflammation</subject><subject>Linkage Disequilibrium</subject><subject>Major histocompatibility complex</subject><subject>Major Histocompatibility Complex - genetics</subject><subject>Malaria</subject><subject>Male</subject><subject>Molecular immunology</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Proteins</subject><subject>Single-nucleotide polymorphism</subject><subject>Tumor necrosis factor</subject><subject>Tumor Necrosis Factor-alpha - genetics</subject><subject>Tumor necrosis factor-TNF</subject><issn>1466-4879</issn><issn>1476-5470</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFktFrFDEQxhdRbK0--yZBUfDhrkk2yW4ej8PaQlXQio8xl51sc-4la7IL7X9vlls4TiwSSELym5lvhq8oXhK8JLisz9N22YKHpSgFw7h-VJwSVokFZxV-PN2FWLC6kifFs5S2GBNBhHxanBDGOREYnxY_12HXd3CHbnXfheG-dwalIY5mGCOgYNFwC8iAH6Lu0KfLNYrQuuCR7bT_5XyLbj5fIOeRRj8gDWhlozPaoz70Y6eHTD4vnljdJXgxn2fF94sPN-vLxfWXj1fr1fXCZCnDosS8IrrRmNRllTtp9GZTAmOSYGk3VuRtIxvMawYCjKWWS8qJlcxQ0XBNyrPi3T5vH8PvMWtRO5cMdFknhDGpilecC8H-CxJJKalxlcE3f4HbMEafm1BUMFLRksmJev0gRWpJKGX0kKrVHSjnbcjzNFNdtSI1lSVneFK2_AeVVwM7Z4IH6_L7UcD7o4DMDHA3tHpMSV19-3rMnu9ZE0NKEazqo9vpeK8IVpOXVNqqyUtq9lKOeDV3Nm520Bz42TwZeDsDOhnd2ai9cenAcUow4ROH91zKX76FeBjRQ7X_AJTj3mk</recordid><startdate>20031001</startdate><enddate>20031001</enddate><creator>Ackerman, H C</creator><creator>Ribas, G</creator><creator>Jallow, M</creator><creator>Mott, R</creator><creator>Neville, M</creator><creator>Sisay-Joof, F</creator><creator>Pinder, M</creator><creator>Campbell, R D</creator><creator>Kwiatkowski, D P</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISR</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20031001</creationdate><title>Complex haplotypic structure of the central MHC region flanking TNF in a West African population</title><author>Ackerman, H C ; Ribas, G ; Jallow, M ; Mott, R ; Neville, M ; Sisay-Joof, F ; Pinder, M ; Campbell, R D ; Kwiatkowski, D P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c551t-30571ada01837008dabb3e449109fbf69fbb9d0584e6ecf2f59251f94c26d5a13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adult</topic><topic>Alleles</topic><topic>Antigens</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Cytokines</topic><topic>Disease</topic><topic>Entropy</topic><topic>Female</topic><topic>full-paper</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Gambia</topic><topic>Gene Expression</topic><topic>Gene Frequency</topic><topic>Gene mapping</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic Markers</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetics, Population</topic><topic>Genotype</topic><topic>Haplotypes</topic><topic>Health aspects</topic><topic>Histocompatibility antigens (hla, h-2 and other systems)</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immunology</topic><topic>Inflammation</topic><topic>Linkage Disequilibrium</topic><topic>Major histocompatibility complex</topic><topic>Major Histocompatibility Complex - genetics</topic><topic>Malaria</topic><topic>Male</topic><topic>Molecular immunology</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Proteins</topic><topic>Single-nucleotide polymorphism</topic><topic>Tumor necrosis factor</topic><topic>Tumor Necrosis Factor-alpha - genetics</topic><topic>Tumor necrosis factor-TNF</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ackerman, H C</creatorcontrib><creatorcontrib>Ribas, G</creatorcontrib><creatorcontrib>Jallow, M</creatorcontrib><creatorcontrib>Mott, R</creatorcontrib><creatorcontrib>Neville, M</creatorcontrib><creatorcontrib>Sisay-Joof, F</creatorcontrib><creatorcontrib>Pinder, M</creatorcontrib><creatorcontrib>Campbell, R D</creatorcontrib><creatorcontrib>Kwiatkowski, D P</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Genes and immunity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ackerman, H C</au><au>Ribas, G</au><au>Jallow, M</au><au>Mott, R</au><au>Neville, M</au><au>Sisay-Joof, F</au><au>Pinder, M</au><au>Campbell, R D</au><au>Kwiatkowski, D P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Complex haplotypic structure of the central MHC region flanking TNF in a West African population</atitle><jtitle>Genes and immunity</jtitle><stitle>Genes Immun</stitle><addtitle>Genes Immun</addtitle><date>2003-10-01</date><risdate>2003</risdate><volume>4</volume><issue>7</issue><spage>476</spage><epage>486</epage><pages>476-486</pages><issn>1466-4879</issn><eissn>1476-5470</eissn><abstract>TNF
polymorphisms have been associated with susceptibility to malaria and other infectious and inflammatory conditions. We investigated a sample of 150 West African chromosomes to determine linkage disequilibrium (LD) between 25 SNP markers located in an 80 kb segment of the MHC Class III region encompassing
TNF
and eight neighbouring genes. We observed 45 haplotypes, and 22 of them comprise 80% of the sample. The pattern of LD is remarkably patchy, such that many markers show no LD with adjacent markers but high LD with markers that are much further away. We introduce a method of examining the implications of LD data for disease association studies based on sample size considerations: this shows that certain
TNF
polymorphisms would be likely to yield positive associations if the true disease allele resided in
LTA
or
BAT1
. We conclude that detailed marker maps are needed to resolve the causal origin of disease associations observed at the
TNF
locus.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>14551600</pmid><doi>10.1038/sj.gene.6364008</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1466-4879 |
| ispartof | Genes and immunity, 2003-10, Vol.4 (7), p.476-486 |
| issn | 1466-4879 1476-5470 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_75755664 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; SpringerLink Journals - AutoHoldings |
| subjects | Adult Alleles Antigens Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Research Cytokines Disease Entropy Female full-paper Fundamental and applied biological sciences. Psychology Fundamental immunology Gambia Gene Expression Gene Frequency Gene mapping Genes Genetic aspects Genetic Markers Genetic Predisposition to Disease Genetics, Population Genotype Haplotypes Health aspects Histocompatibility antigens (hla, h-2 and other systems) Human Genetics Humans Immune response Immunology Inflammation Linkage Disequilibrium Major histocompatibility complex Major Histocompatibility Complex - genetics Malaria Male Molecular immunology Polymorphism, Single Nucleotide Proteins Single-nucleotide polymorphism Tumor necrosis factor Tumor Necrosis Factor-alpha - genetics Tumor necrosis factor-TNF |
| title | Complex haplotypic structure of the central MHC region flanking TNF in a West African population |
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