连锁分析表明，3p14 - 13区域对多发性硬化症具有重要意义。

Linkage analysis suggests a region of importance for multiple sclerosis in 3p14-13.

作者信息

Dai Y, Xu C, Holmberg M, Oturai A, Fredrikson S, Sandberg-Wollheim M, Laaksonen M, Spurkland A, Myhr K M, Ryder L P, Sorensen P S, Svejgaard A, Hillert J

机构信息

Department of Neurology, Huddinge University Hospital, Karolinska Institutet, Huddinge, Sweden.

出版信息

Genes Immun. 2001 Dec;2(8):451-4. doi: 10.1038/sj.gene.6363805.

DOI:10.1038/sj.gene.6363805

PMID:11781712

Abstract

Four genomic screens for linkage in multiple sclerosis (MS) have been reported. They confirmed the established role of the human leucocyte antigen (HLA) complex genes in MS and, in addition, suggested the importance of a few other chromosomal segments. Here we report evidence for the importance of 3p14-13 region identified by suggestive linkage in genomic screens from Canada and the United Kingdom. When studying 146 Nordic MS multiplex families, mostly affected sib-pairs, with eight microsatellite markers, spanning a 36-cM region, we observed a two-point non-parametric linkage (NPL) score of 2.39 (P = 0.007) by the GENEHUNTER package for marker D3S1285 and a multipoint NPL score of 1.20 in the same region. Association studies in Swedish MS patients revealed modest allelic associations of uncertain significance not supported by transmission analysis. Analysis of the trinucleotide repeat sequence of the SCA7 gene in Swedish index cases did not reveal expansions. We conclude that support was obtained for the location of a gene or genes with importance for MS susceptibility in 3p14-13 region.

摘要

已经报道了四项针对多发性硬化症（MS）的连锁基因组筛查。这些筛查证实了人类白细胞抗原（HLA）复合体基因在MS中的既定作用，此外，还提示了其他一些染色体片段的重要性。在此，我们报告了在加拿大和英国的基因组筛查中通过提示性连锁鉴定出的3p14 - 13区域重要性的证据。在研究146个北欧MS多病例家系（大多为患病同胞对）时，使用跨越36厘摩区域的8个微卫星标记，我们通过GENEHUNTER软件包观察到标记D3S1285的两点非参数连锁（NPL）得分为2.39（P = 0.007），且在同一区域的多点NPL得分为1.20。对瑞典MS患者的关联研究显示，存在意义不确定的适度等位基因关联，但未得到传递分析的支持。对瑞典先证者中SCA7基因三核苷酸重复序列的分析未发现扩增。我们得出结论，支持在3p14 - 13区域存在对MS易感性具有重要意义的一个或多个基因。