Dyment D A, Willer C J, Scott B, Armstrong H, Ligers A, Hillert J, Paty D W, Hashimoto S, Devonshire V, Hooge J, Kastrukoff L, Oger J, Metz L, Warren S, Hader W, Power C, Auty A, Nath A, Nelson R, Freedman M, Brunet D, Paulseth J E, Rice G, O'Connor P, Duquette P, Lapierre Y, Francis G, Bouchard J P, Murray T J, Bhan V, Maxner C, Pryse-Phillips W, Stefanelli M, Sadovnick A D, Risch N, Ebers G C
The Wellcome Trust Center for Human Genetics, Oxford, UK.
Neurogenetics. 2001 Jul;3(3):145-51. doi: 10.1007/s100480100113.
Four published genome screens have identified a number of markers with increased sharing in multiple sclerosis (MS) families, although none has reached statistical significance. One hundred and five markers previously identified as showing increased sharing in Canadian, British, Finnish, and American genome screens were genotyped in 219 sibling pairs ascertained from the database of the Canadian Collaborative Project on Genetic Susceptibility to MS (CCPGSMS). No markers examined met criteria for significant linkage. Markers located at 5p14 and 17q22 were analyzed in a total of 333 sibling pairs and attained mlod scores of 2.27 and 1.14, respectively. The known HLA Class II DRB1 association with MS was confirmed (P<0.0001). Significant transmission disequilibrium was also observed for D17S789 at 17q22 (P=0.0015). This study highlights the difficulty of searching for genes with only mild-to-moderate effects on susceptibility, although large effects of specific loci may still be present in individual families. Future progress in the genetics of this complex trait may be helped by (1) focussing on more ethnically homogeneous samples, (2) using an increased number of MS families, and (3) using transmission disequilibrium analysis in candidate regions rather than the affected relative pair linkage analysis.
四项已发表的全基因组筛查已经在多发性硬化症（MS）家族中发现了一些共享增加的标记物，尽管没有一个达到统计学显著性。在从加拿大MS遗传易感性合作项目（CCPGSMS）数据库中确定的219对同胞对中，对先前在加拿大、英国、芬兰和美国全基因组筛查中确定为共享增加的105个标记物进行了基因分型。所检测的标记物均未达到显著连锁的标准。位于5p14和17q22的标记物在总共333对同胞对中进行了分析，其最大优势对数（mlod）得分分别为2.27和1.14。已知的HLA II类DRB1与MS的关联得到了证实（P<0.0001）。在17q22处的D17S789也观察到显著的传递不平衡（P=0.0015）。这项研究突出了寻找对易感性只有轻度至中度影响的基因的困难，尽管特定基因座的大效应可能仍存在于个别家族中。（1）关注种族更同质的样本，（2）使用更多的MS家族，以及（3）在候选区域使用传递不平衡分析而非受累亲属对连锁分析，可能有助于这一复杂性状遗传学的未来进展。
