Wood N W, Sawcer S J, Kellar-Wood H F, Holmans P, Clayton D, Robertson N, Compston D A
University of Cambridge Neurology unit, Addenbrooke's Hospital, UK.
J Neurol. 1995 Oct;242(10):677-82. doi: 10.1007/BF00866919.
A haplotype marker consisting of three biallelic restriction fragment length polymorphism (RFLP) loci from the VH-2 variable gene family was examined in 124 families with sibling pairs concordant for multiple sclerosis, 178 unrelated patients and 159 unaffected controls to investigate the role of the immunoglobulin heavy chain gene cluster in susceptibility to multiple sclerosis. Evidence for linkage was assessed using the affected sibling pair method of identity by descent, modified to allow for haplotype sharing on a probabilistic basis in families where haplotypes could not be assigned with certainty. The estimated probabilities of affected siblings sharing 0, 1 or 2 haplotypes were Z0 = 0.20, Z1 = 0.45, Z2 = 0.35. This deviation from the expected sharing probabilities of Z0 = 0.25, Z1 = 0.5, Z2 = 0.25 provides evidence for weak linkage (P < 0.05; equivalent to a lod score of 0.84); however, no significant allelic or haplotypic association was observed. Linkage without a population association suggests that a gene encoded on 14q confers susceptibility to multiple sclerosis, although this is not any of the existing VH-2 polymorphisms.
对一个由来自VH-2可变基因家族的三个双等位基因限制性片段长度多态性（RFLP）位点组成的单倍型标记进行了检测，检测对象包括124个有患多发性硬化症同胞对的家庭、178名无亲缘关系的患者以及159名未患病的对照者，以研究免疫球蛋白重链基因簇在多发性硬化症易感性中的作用。采用基于家系的同胞对身份相同性方法评估连锁证据，并进行了修改，以便在无法确定单倍型的家庭中基于概率考虑单倍型共享情况。患病同胞共享0、1或2个单倍型的估计概率分别为Z0 = 0.20、Z1 = 0.45、Z2 = 0.35。这与预期的共享概率Z0 = 0.25、Z1 = 0.5、Z2 = 0.25存在偏差，为弱连锁提供了证据（P < 0.05；相当于lod分数为0.84）；然而，未观察到显著的等位基因或单倍型关联。无群体关联的连锁表明，14q上编码的一个基因赋予了多发性硬化症易感性，尽管这不是现有的任何VH-2多态性。
