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.

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