Evidence of Linkage with HLA-DR in DRB115-Negative Families with Multiple Sclerosis
The importance of the HLA-DR locus to multiple sclerosis (MS) susceptibility was assessed in 542 sib pairs with MS and in their families. By genotyping 1,978 individuals for HLA-DRB1 alleles, we confirmed the well-established association of MS with HLA-DRB1*15 ( HLA-DRB1*1501 and HLA-DRB5*0101), by...
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| Veröffentlicht in: | American journal of human genetics 2001-10, Vol.69 (4), p.900-903 |
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| container_title | American journal of human genetics |
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| creator | Ligers, Arturs Dyment, David A. Willer, Cristen J. Sadovnick, A. Dessa Ebers, George Risch, Neil Hillert, Jan |
| description | The importance of the HLA-DR locus to multiple sclerosis (MS) susceptibility was assessed in 542 sib pairs with MS and in their families. By genotyping 1,978 individuals for HLA-DRB1 alleles, we confirmed the well-established association of MS with HLA-DRB1*15 (
HLA-DRB1*1501 and
HLA-DRB5*0101), by the transmission/disequilibrium test (χ
2=138.3;
P |
| doi_str_mv | 10.1086/323480 |
| format | Article |
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HLA-DRB1*1501 and
HLA-DRB5*0101), by the transmission/disequilibrium test (χ
2=138.3;
P<.0001). We obtained significant evidence of linkage throughout the whole data set (
mlod=4.09; 59.9% sharing). Surprisingly, similar sharing was also observed in 58 families in which both parents lacked the DRB1*15 allele (
mlod=1.56; 62.7% sharing;
P=.0081). Our findings suggest that the notion that HLA-DRB1*15 is the sole major-histocompatibility-complex determinant of susceptibility in northern-European populations with MS may be incorrect. It remains possible that the association of MS with HLA-DRB1*15 is due to linkage disequilibrium with a nearby locus and/or to the presence of disease-influencing allele(s) in DRB1*15-negative haplotypes.</description><identifier>ISSN: 0002-9297</identifier><identifier>EISSN: 1537-6605</identifier><identifier>DOI: 10.1086/323480</identifier><identifier>PMID: 11519010</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Alleles ; Chromosome Mapping ; Gene Frequency - genetics ; Genetic Linkage - genetics ; Genetic Predisposition to Disease - genetics ; Haplotypes - genetics ; histocompatibility antigen HLA ; HLA-DR Antigens - genetics ; HLA-DRB1 Chains ; Humans ; Linkage Disequilibrium - genetics ; Medicin och hälsovetenskap ; Multiple Sclerosis - genetics ; Nuclear Family</subject><ispartof>American journal of human genetics, 2001-10, Vol.69 (4), p.900-903</ispartof><rights>2001 The American Society of Human Genetics</rights><rights>2001 by The American Society of Human Genetics. All rights reserved. 2001</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c520t-e17cdf67bed26eec8296428258ad88c090a86342e83b36f33fc875e0f4ec983c3</citedby><cites>FETCH-LOGICAL-c520t-e17cdf67bed26eec8296428258ad88c090a86342e83b36f33fc875e0f4ec983c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1226077/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://dx.doi.org/10.1086/323480$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,552,727,780,784,885,3550,27924,27925,45995,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11519010$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:1941319$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Ligers, Arturs</creatorcontrib><creatorcontrib>Dyment, David A.</creatorcontrib><creatorcontrib>Willer, Cristen J.</creatorcontrib><creatorcontrib>Sadovnick, A. Dessa</creatorcontrib><creatorcontrib>Ebers, George</creatorcontrib><creatorcontrib>Risch, Neil</creatorcontrib><creatorcontrib>Hillert, Jan</creatorcontrib><creatorcontrib>the Canadian Collaborative Study Groups</creatorcontrib><creatorcontrib>Canadian Collaborative Study Groups</creatorcontrib><title>Evidence of Linkage with HLA-DR in DRB115-Negative Families with Multiple Sclerosis</title><title>American journal of human genetics</title><addtitle>Am J Hum Genet</addtitle><description>The importance of the HLA-DR locus to multiple sclerosis (MS) susceptibility was assessed in 542 sib pairs with MS and in their families. By genotyping 1,978 individuals for HLA-DRB1 alleles, we confirmed the well-established association of MS with HLA-DRB1*15 (
HLA-DRB1*1501 and
HLA-DRB5*0101), by the transmission/disequilibrium test (χ
2=138.3;
P<.0001). We obtained significant evidence of linkage throughout the whole data set (
mlod=4.09; 59.9% sharing). Surprisingly, similar sharing was also observed in 58 families in which both parents lacked the DRB1*15 allele (
mlod=1.56; 62.7% sharing;
P=.0081). Our findings suggest that the notion that HLA-DRB1*15 is the sole major-histocompatibility-complex determinant of susceptibility in northern-European populations with MS may be incorrect. It remains possible that the association of MS with HLA-DRB1*15 is due to linkage disequilibrium with a nearby locus and/or to the presence of disease-influencing allele(s) in DRB1*15-negative haplotypes.</description><subject>Alleles</subject><subject>Chromosome Mapping</subject><subject>Gene Frequency - genetics</subject><subject>Genetic Linkage - genetics</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Haplotypes - genetics</subject><subject>histocompatibility antigen HLA</subject><subject>HLA-DR Antigens - genetics</subject><subject>HLA-DRB1 Chains</subject><subject>Humans</subject><subject>Linkage Disequilibrium - genetics</subject><subject>Medicin och hälsovetenskap</subject><subject>Multiple Sclerosis - genetics</subject><subject>Nuclear Family</subject><issn>0002-9297</issn><issn>1537-6605</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNqFkltv1DAQhS1ERZcCPwHlibfA2E58eUEqvVCkBaQWni2vM9kOzSZbO7sV_x5XWboUCfHkkec7R6OZw9grDm85GPVOClkZeMJmvJa6VArqp2wGAKK0wupD9jylHwCcG5DP2CHnNbfAYcauzrbUYB-wGNpiTv2NX2JxR-N1cTE_Lk8vC-qL08sPWVB-waUfaYvFuV9RR5gm7vOmG2ndYXEVOoxDovSCHbS-S_hy9x6x7-dn304uyvnXj59OjudlqAWMJXIdmlbpBTZCIQYjrKqEEbXxjTEBLHijZCXQyIVUrZRtMLpGaCsM1sggj1g5-aY7XG8Wbh1p5eNPN3hyu6-bXKGrrTK6yrz-J7-OQ7MX_RZyW3HJbVa-n5S5vcImYD9G3z02eNTp6doth63jQijQOhu82RnE4XaDaXQrSgG7zvc4bJLTecGgwP4X5EbWVaVhD4a88xSxfZiGg7uPhJsikcHXf86-x3YZyABMAOZbbQmjS4HuI9FQxDC6ZqC_PX8BVt_BDQ</recordid><startdate>20011001</startdate><enddate>20011001</enddate><creator>Ligers, Arturs</creator><creator>Dyment, David A.</creator><creator>Willer, Cristen J.</creator><creator>Sadovnick, A. Dessa</creator><creator>Ebers, George</creator><creator>Risch, Neil</creator><creator>Hillert, Jan</creator><general>Elsevier Inc</general><general>The American Society of Human Genetics</general><scope>6I.</scope><scope>AAFTH</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>7TK</scope><scope>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20011001</creationdate><title>Evidence of Linkage with HLA-DR in DRB115-Negative Families with Multiple Sclerosis</title><author>Ligers, Arturs ; Dyment, David A. ; Willer, Cristen J. ; Sadovnick, A. Dessa ; Ebers, George ; Risch, Neil ; Hillert, Jan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c520t-e17cdf67bed26eec8296428258ad88c090a86342e83b36f33fc875e0f4ec983c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Alleles</topic><topic>Chromosome Mapping</topic><topic>Gene Frequency - genetics</topic><topic>Genetic Linkage - genetics</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Haplotypes - genetics</topic><topic>histocompatibility antigen HLA</topic><topic>HLA-DR Antigens - genetics</topic><topic>HLA-DRB1 Chains</topic><topic>Humans</topic><topic>Linkage Disequilibrium - genetics</topic><topic>Medicin och hälsovetenskap</topic><topic>Multiple Sclerosis - genetics</topic><topic>Nuclear Family</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ligers, Arturs</creatorcontrib><creatorcontrib>Dyment, David A.</creatorcontrib><creatorcontrib>Willer, Cristen J.</creatorcontrib><creatorcontrib>Sadovnick, A. Dessa</creatorcontrib><creatorcontrib>Ebers, George</creatorcontrib><creatorcontrib>Risch, Neil</creatorcontrib><creatorcontrib>Hillert, Jan</creatorcontrib><creatorcontrib>the Canadian Collaborative Study Groups</creatorcontrib><creatorcontrib>Canadian Collaborative Study Groups</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>American journal of human genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ligers, Arturs</au><au>Dyment, David A.</au><au>Willer, Cristen J.</au><au>Sadovnick, A. Dessa</au><au>Ebers, George</au><au>Risch, Neil</au><au>Hillert, Jan</au><aucorp>the Canadian Collaborative Study Groups</aucorp><aucorp>Canadian Collaborative Study Groups</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evidence of Linkage with HLA-DR in DRB115-Negative Families with Multiple Sclerosis</atitle><jtitle>American journal of human genetics</jtitle><addtitle>Am J Hum Genet</addtitle><date>2001-10-01</date><risdate>2001</risdate><volume>69</volume><issue>4</issue><spage>900</spage><epage>903</epage><pages>900-903</pages><issn>0002-9297</issn><eissn>1537-6605</eissn><abstract>The importance of the HLA-DR locus to multiple sclerosis (MS) susceptibility was assessed in 542 sib pairs with MS and in their families. By genotyping 1,978 individuals for HLA-DRB1 alleles, we confirmed the well-established association of MS with HLA-DRB1*15 (
HLA-DRB1*1501 and
HLA-DRB5*0101), by the transmission/disequilibrium test (χ
2=138.3;
P<.0001). We obtained significant evidence of linkage throughout the whole data set (
mlod=4.09; 59.9% sharing). Surprisingly, similar sharing was also observed in 58 families in which both parents lacked the DRB1*15 allele (
mlod=1.56; 62.7% sharing;
P=.0081). Our findings suggest that the notion that HLA-DRB1*15 is the sole major-histocompatibility-complex determinant of susceptibility in northern-European populations with MS may be incorrect. It remains possible that the association of MS with HLA-DRB1*15 is due to linkage disequilibrium with a nearby locus and/or to the presence of disease-influencing allele(s) in DRB1*15-negative haplotypes.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>11519010</pmid><doi>10.1086/323480</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | American journal of human genetics, 2001-10, Vol.69 (4), p.900-903 |
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| source | MEDLINE; Cell Press Free Archives; SWEPUB Freely available online; PubMed (Medline); Access via ScienceDirect (Elsevier); EZB Electronic Journals Library |
| subjects | Alleles Chromosome Mapping Gene Frequency - genetics Genetic Linkage - genetics Genetic Predisposition to Disease - genetics Haplotypes - genetics histocompatibility antigen HLA HLA-DR Antigens - genetics HLA-DRB1 Chains Humans Linkage Disequilibrium - genetics Medicin och hälsovetenskap Multiple Sclerosis - genetics Nuclear Family |
| title | Evidence of Linkage with HLA-DR in DRB115-Negative Families with Multiple Sclerosis |
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