• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >HLA class I alleles tag HLA-DRB1~*1501 haplotypes for differential risk in multiple sclerosis susceptibility
【24h】

HLA class I alleles tag HLA-DRB1~*1501 haplotypes for differential risk in multiple sclerosis susceptibility

机译：HLA I类等位基因标记HLA-DRB1〜* 1501单倍型用于多发性硬化易感性的差异风险

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The major locus for multiple sclerosis (MS) susceptibility is located within the class II region of the Major Histocompatibility Complex (MHC). HLA-DRB1 alleles, constituting the strongest MS susceptibility factors, have been widely exploited in research including construction of transgenic animal models of MS. Many studies have concluded that HLA-DRB1~*15 allele itself determines MS-associated susceptibility. If this were true, haplotypes bearing this allele would confer equal risk. If HLA-DRB1*15 bearing haplotypes differed for risk, roles for other loci in this region would be implied and further study of the fine structure of this locus would be compelling. We have tested the hypothesis comparing haplotypes stratified by HLA class I tagging. We show here that HLA-DRB1~*15-bearing-haplotypes in 1970 individuals from 494 MS families are indeed heterogeneous. Some HLA-DRB1~*15 haplotypes determine susceptibility while others do not. Three groups of class I tagged HLA-DRB1~*15 haplotypes were not over-transmitted: (ⅰ) HLA-DRB1~*15-HLA-B~*08 (TR = 25, NT = 23, Odds Ratio = 1.09), (ⅱ) -HLA-B~*27 (TR = 18, NT = 17, Odds Ratio = 1.06), and (ⅲ) rare HLA-DRB1~*15 haplotypes (frequency <0.02). Rare haplotypes were significantly different from common haplotypes, and transmissions were remarkably similar to those for class-l-matched non-HLA-DRB1~*15 haplotypes. These results unambiguously indicate that HLA-DRB1~*15 is part of a susceptibility haplotype but cannot be the susceptibility allele itself, requiring either epistatic interactions, epigenetic modifications on some haplotypes, or nearby structural variation. These findings strongly imply that differences among HLA-DRB1~*15 haplotypes will furnish the basis for MHC-associated susceptibility in MS and raise the possibility that the MHC haplotype is the fundamental unit of genetic control of immune response.
机译：多发性硬化症（MS）易感性的主要基因座位于主要组织相容性复合体（MHC）的II类区域内。构成最强MS易感性因子的HLA-DRB1等位基因已在包括MS的转基因动物模型构建在内的研究中得到广泛利用。许多研究已经得出结论，HLA-DRB1〜* 15等位基因本身决定了MS相关的易感性。如果是这样，则带有该等位基因的单倍型将赋予相同的风险。如果携带HLA-DRB1 * 15的单倍型在风险上有所不同，则将暗示该区域其他位点的作用，并且对该位点精细结构的进一步研究将具有说服力。我们已经测试了比较由HLA I类标签分层的单倍型的假设。我们在这里显示，来自494个MS家庭的1970年个体中的HLA-DRB1〜* 15-轴承单倍型确实是异质的。一些HLA-DRB1〜* 15单倍型决定了易感性，而另一些则没有。三类I类标记的HLA-DRB1〜* 15单倍型未过度传播：（ⅰ）HLA-DRB1〜* 15-HLA-B〜* 08（TR = 25，NT = 23，几率= 1.09）， （ⅱ）-HLA-B〜* 27（TR = 18，NT = 17，奇数比= 1.06），（ⅲ）稀有HLA-DRB1〜* 15单倍型（频率<0.02）。罕见的单倍型与普通的单倍型显着不同，并且传播与与I类匹配的非HLA-DRB1〜* 15单倍型的传递显着相似。这些结果明确表明，HLA-DRB1〜* 15是易感性单倍型的一部分，但不能是易感性等位基因本身，需要上位相互作用，某些单倍型的表观遗传修饰或附近的结构变异。这些发现强烈暗示HLA-DRB1〜* 15单倍型之间的差异将为MS中MHC相关的敏感性提供基础，并增加MHC单倍型是免疫应答遗传控制的基本单位的可能性。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号