Linkage disequilibrium analysis of chromosome 12q14–15 in multiple sclerosis: delineation of a 118-kb interval around interferon-γ (IFNG) that is involved in male versus female differential susceptibility
We have recently reported the association of a polymorphic intronic CA-repeat in the interferon-gamma gene (IFNG) with gender bias in susceptibility to multiple sclerosis (MS) in a Sardinian population. This association could refer to a functional polymorphism within IFNG or could be due to linkage...
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| Veröffentlicht in: | Genes and immunity 2002-12, Vol.3 (8), p.470-476 |
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| creator | Goris, A Heggarty, S Marrosu, M G Graham, C Billiau, A Vandenbroeck, K |
| description | We have recently reported the association of a polymorphic intronic CA-repeat in the interferon-gamma gene (IFNG) with gender bias in susceptibility to multiple sclerosis (MS) in a Sardinian population. This association could refer to a functional polymorphism within IFNG or could be due to linkage disequilibrium between the IFNG marker and a neighbouring susceptibility locus. Within the average reach of linkage disequilibrium, various other candidate genes are located. Among these the most striking ones are the genes coding for the cytokines interleukin-22 (IL-22) and interleukin-26 (IL-26) that constitute together with IFNG a cytokine cluster on chromosome 12q14. To determine more precisely the location of this gender-associated susceptibility locus, we have now performed a more extensive linkage disequilibrium screen of this region using nine additional microsatellite markers. This locus appeared to be confined to a 118-kb interval that is bordered by the markers D12S313 and D12S2511, in which IFNG itself remains the main candidate gene. Haplotype analysis confirmed that this MS-associated locus protects males from developing MS according to a recessive or allele-dosage model. Our results indicate that the well-documented gender differences in susceptibility to MS are at least partially caused by genetic factors in the region surrounding IFNG. |
| doi_str_mv | 10.1038/sj.gene.6363913 |
| format | Article |
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This association could refer to a functional polymorphism within IFNG or could be due to linkage disequilibrium between the IFNG marker and a neighbouring susceptibility locus. Within the average reach of linkage disequilibrium, various other candidate genes are located. Among these the most striking ones are the genes coding for the cytokines interleukin-22 (IL-22) and interleukin-26 (IL-26) that constitute together with IFNG a cytokine cluster on chromosome 12q14. To determine more precisely the location of this gender-associated susceptibility locus, we have now performed a more extensive linkage disequilibrium screen of this region using nine additional microsatellite markers. This locus appeared to be confined to a 118-kb interval that is bordered by the markers D12S313 and D12S2511, in which IFNG itself remains the main candidate gene. Haplotype analysis confirmed that this MS-associated locus protects males from developing MS according to a recessive or allele-dosage model. Our results indicate that the well-documented gender differences in susceptibility to MS are at least partially caused by genetic factors in the region surrounding IFNG.</description><identifier>ISSN: 1466-4879</identifier><identifier>EISSN: 1476-5470</identifier><identifier>DOI: 10.1038/sj.gene.6363913</identifier><identifier>PMID: 12486605</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Adolescent ; Adult ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Chromosome 12 ; Chromosomes, Human, Pair 12 - genetics ; Cytokines ; Female ; full-paper ; Gender ; Gene Expression ; Genes ; Genetic aspects ; Genetic factors ; Genetic markers ; Genetic Predisposition to Disease - genetics ; Genetic susceptibility ; Haplotypes ; Health aspects ; Human Genetics ; Humans ; Immunology ; Interferon gamma ; Interferon-gamma - genetics ; Interleukin 22 ; Linkage (Genetics) ; Linkage analysis ; Linkage disequilibrium ; Linkage Disequilibrium - genetics ; Male ; Microsatellites ; Multiple sclerosis ; Multiple Sclerosis - genetics ; Physiological aspects ; Risk factors ; Sex Characteristics ; Sex differences ; Susceptibility ; γ-Interferon</subject><ispartof>Genes and immunity, 2002-12, Vol.3 (8), p.470-476</ispartof><rights>Macmillan Publishers Limited 2002</rights><rights>COPYRIGHT 2002 Nature Publishing Group</rights><rights>Macmillan Publishers Limited 2002.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c494t-4535a3db263ac3a91d98ebf67c045a0d9e21348443924605939d8408de83053d3</citedby><cites>FETCH-LOGICAL-c494t-4535a3db263ac3a91d98ebf67c045a0d9e21348443924605939d8408de83053d3</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.6363913$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.gene.6363913$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12486605$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Goris, A</creatorcontrib><creatorcontrib>Heggarty, S</creatorcontrib><creatorcontrib>Marrosu, M G</creatorcontrib><creatorcontrib>Graham, C</creatorcontrib><creatorcontrib>Billiau, A</creatorcontrib><creatorcontrib>Vandenbroeck, K</creatorcontrib><title>Linkage disequilibrium analysis of chromosome 12q14–15 in multiple sclerosis: delineation of a 118-kb interval around interferon-γ (IFNG) that is involved in male versus female differential susceptibility</title><title>Genes and immunity</title><addtitle>Genes Immun</addtitle><addtitle>Genes Immun</addtitle><description>We have recently reported the association of a polymorphic intronic CA-repeat in the interferon-gamma gene (IFNG) with gender bias in susceptibility to multiple sclerosis (MS) in a Sardinian population. This association could refer to a functional polymorphism within IFNG or could be due to linkage disequilibrium between the IFNG marker and a neighbouring susceptibility locus. Within the average reach of linkage disequilibrium, various other candidate genes are located. Among these the most striking ones are the genes coding for the cytokines interleukin-22 (IL-22) and interleukin-26 (IL-26) that constitute together with IFNG a cytokine cluster on chromosome 12q14. To determine more precisely the location of this gender-associated susceptibility locus, we have now performed a more extensive linkage disequilibrium screen of this region using nine additional microsatellite markers. This locus appeared to be confined to a 118-kb interval that is bordered by the markers D12S313 and D12S2511, in which IFNG itself remains the main candidate gene. Haplotype analysis confirmed that this MS-associated locus protects males from developing MS according to a recessive or allele-dosage model. Our results indicate that the well-documented gender differences in susceptibility to MS are at least partially caused by genetic factors in the region surrounding IFNG.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Chromosome 12</subject><subject>Chromosomes, Human, Pair 12 - genetics</subject><subject>Cytokines</subject><subject>Female</subject><subject>full-paper</subject><subject>Gender</subject><subject>Gene Expression</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic factors</subject><subject>Genetic markers</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genetic susceptibility</subject><subject>Haplotypes</subject><subject>Health aspects</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Immunology</subject><subject>Interferon gamma</subject><subject>Interferon-gamma - 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genetics</topic><topic>Cytokines</topic><topic>Female</topic><topic>full-paper</topic><topic>Gender</topic><topic>Gene Expression</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic factors</topic><topic>Genetic markers</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Genetic susceptibility</topic><topic>Haplotypes</topic><topic>Health aspects</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Immunology</topic><topic>Interferon gamma</topic><topic>Interferon-gamma - genetics</topic><topic>Interleukin 22</topic><topic>Linkage (Genetics)</topic><topic>Linkage analysis</topic><topic>Linkage disequilibrium</topic><topic>Linkage Disequilibrium - genetics</topic><topic>Male</topic><topic>Microsatellites</topic><topic>Multiple sclerosis</topic><topic>Multiple Sclerosis - genetics</topic><topic>Physiological aspects</topic><topic>Risk factors</topic><topic>Sex Characteristics</topic><topic>Sex differences</topic><topic>Susceptibility</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Goris, A</creatorcontrib><creatorcontrib>Heggarty, S</creatorcontrib><creatorcontrib>Marrosu, M G</creatorcontrib><creatorcontrib>Graham, C</creatorcontrib><creatorcontrib>Billiau, A</creatorcontrib><creatorcontrib>Vandenbroeck, K</creatorcontrib><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>Goris, A</au><au>Heggarty, S</au><au>Marrosu, M G</au><au>Graham, C</au><au>Billiau, A</au><au>Vandenbroeck, K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Linkage disequilibrium analysis of chromosome 12q14–15 in multiple sclerosis: delineation of a 118-kb interval around interferon-γ (IFNG) that is involved in male versus female differential susceptibility</atitle><jtitle>Genes and immunity</jtitle><stitle>Genes Immun</stitle><addtitle>Genes Immun</addtitle><date>2002-12-01</date><risdate>2002</risdate><volume>3</volume><issue>8</issue><spage>470</spage><epage>476</epage><pages>470-476</pages><issn>1466-4879</issn><eissn>1476-5470</eissn><abstract>We have recently reported the association of a polymorphic intronic CA-repeat in the interferon-gamma gene (IFNG) with gender bias in susceptibility to multiple sclerosis (MS) in a Sardinian population. This association could refer to a functional polymorphism within IFNG or could be due to linkage disequilibrium between the IFNG marker and a neighbouring susceptibility locus. Within the average reach of linkage disequilibrium, various other candidate genes are located. Among these the most striking ones are the genes coding for the cytokines interleukin-22 (IL-22) and interleukin-26 (IL-26) that constitute together with IFNG a cytokine cluster on chromosome 12q14. To determine more precisely the location of this gender-associated susceptibility locus, we have now performed a more extensive linkage disequilibrium screen of this region using nine additional microsatellite markers. This locus appeared to be confined to a 118-kb interval that is bordered by the markers D12S313 and D12S2511, in which IFNG itself remains the main candidate gene. Haplotype analysis confirmed that this MS-associated locus protects males from developing MS according to a recessive or allele-dosage model. Our results indicate that the well-documented gender differences in susceptibility to MS are at least partially caused by genetic factors in the region surrounding IFNG.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>12486605</pmid><doi>10.1038/sj.gene.6363913</doi><tpages>7</tpages></addata></record> |
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| subjects | Adolescent Adult Biomedical and Life Sciences Biomedicine Cancer Research Chromosome 12 Chromosomes, Human, Pair 12 - genetics Cytokines Female full-paper Gender Gene Expression Genes Genetic aspects Genetic factors Genetic markers Genetic Predisposition to Disease - genetics Genetic susceptibility Haplotypes Health aspects Human Genetics Humans Immunology Interferon gamma Interferon-gamma - genetics Interleukin 22 Linkage (Genetics) Linkage analysis Linkage disequilibrium Linkage Disequilibrium - genetics Male Microsatellites Multiple sclerosis Multiple Sclerosis - genetics Physiological aspects Risk factors Sex Characteristics Sex differences Susceptibility γ-Interferon |
| title | Linkage disequilibrium analysis of chromosome 12q14–15 in multiple sclerosis: delineation of a 118-kb interval around interferon-γ (IFNG) that is involved in male versus female differential susceptibility |
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