In addition to the 129-derived segments, in both cohorts the C57BL/6 strain contributed to the autoimmune traits with one major susceptibility locus on Chromosome 3. A genomic region between D3Mit40 and D3Mit13, with an estimated peak at position approximately 51 cM, showed a significant linkage to ANA production and weaker linkages to anti-ssDNA and anti-chromatin production (see Table 3; Figure 7). The high frequency of autoimmune phenotype in the (129 × C57BL/6) hybrid genetic background and its absence in either of the inbred parental strains imply that there are essential interactions between 129- and C57BL/6-derived alleles for the expression of autoimmunity. We investigated further the effects of genes from the C57BL/6 background by repeating the linkage analysis in (129 × C57BL/6)F2 mice, whilst controlling for the very strong 129 effect on distal Chromosome 1, as previously described (Zeng 1994). The results of this analysis showed that the statistical support for the linkage of the C57BL/6 locus on Chromosome 3 for ANA increased from logarithm of odds (LOD) 5.4 to LOD 6.4.