Miakotkin V A, Finogenova S A, Sharapova E P, Guseva I A, Moshnina M A, Alekseeva L I
Genetika. 1996 Jul;32(7):985-9.
Based on consistent associations of rheumatoid arthritis (RA) with some HLA antigens several authors hypothesized the existence of a gene of susceptibility to RA, linked closely with the HLA loci and in disequilibrium with associated alleles. Data on six pedigrees (four of these involved three generations) with recurrent diseases (in total, 45 individuals, 13 of whom were affected with RA) were used in the linkage analysis. The data on allelic typing of HLA-A and -B loci were combined to form a "superlocus" that enabled more accurate determination of an individual genotype for the marker. Previously obtained parameters of disease inheritance were used to test the locus: a frequency of the abnormal allele of 2.14%, and the penetrances of abnormal homozygotes, heterozygotes, and normal homozygotes of 100, 2.1, and 0% in men and 100, 6, and 0.3% in, respectively. A softwares package developed in the Department of Epidemiology and Genetics of the Institute of Rheumatology, Russian Academy of Medical Sciences, was used in the linkage analysis. This work resulted in two-dimensional tables of Lod score values at different recombination frequencies (RF), changing with a step of 0.05 in men and women. The minimal Lord score value at RF = 0 is -2.11, which is higher than the critical value (-2.0) and serves as an indication of the absence of close linkage between the analyzed loci.
基于类风湿关节炎（RA）与某些HLA抗原之间的一致关联，一些作者推测存在RA易感基因，该基因与HLA基因座紧密相连且与相关等位基因处于不平衡状态。连锁分析使用了六个有复发性疾病的家系（其中四个涉及三代人）的数据（总共45人，其中13人患有RA）。将HLA - A和 - B基因座的等位基因分型数据合并形成一个“超级基因座”，以便更准确地确定个体的标记基因型。使用先前获得的疾病遗传参数来检验该基因座：异常等位基因频率为2.14%，男性中异常纯合子、杂合子和正常纯合子的外显率分别为100%、2.1%和0%，女性中分别为100%、6%和0.3%。连锁分析使用了俄罗斯医学科学院风湿病研究所流行病学和遗传学系开发的软件包。这项工作得出了不同重组频率（RF）下男性和女性的Lod评分值的二维表，RF以0.05的步长变化。RF = 0时的最小Lod评分值为 - 2.11，高于临界值（-2.0），这表明所分析的基因座之间不存在紧密连锁。
