Analysis of linkage between the major histocompatibility system and juvenile, insulin-dependent diabetes in multiplex families. Reanalysis of data.

Linkage Analysis between the Major Histocompatibility System and Insulin-dependent Diabetes in Families with Patients in Two Consecutive Generations

“…In such a suibset of patienits (about 11% of all famnilies with one child affected. ),2 we presented evidence for the existence of linkage of -13 map Units between the 1ILA and the assumied diabetic locuis (9). On the other hanid, the MG families (about 5% of all families with one child affected)2 ascertainied to imiaximize the likelihood of a genetically homnogenieouis formn ( inheritance of this gene is more likely to be dominant, because in 26 of the 28 families we observed parent to child transmission of the trait.…”

“…Conversely, the same method applied to the families published by Rubinstein et al (10), reportedly ascertained at random, showed a lod score of 0.88, thus failing to indicate linkage between the HLA and IDDM (9). This suggests that our findings of linkage imay be specific for the specially selected families studied by Us (1,9), and may not be applicable to famnilies ascertained at randomn or according to other criteria. Furthermnore, it does not confirmi the claim of Rubenstein et al (10) that all IDDM cases are autosomal recessive.…”

“…These families were selected to maximize the proportion of cases with an autosomial recessive mode of inheritance. Assuming this genetic mode, when using the lod (the logarithm of odds) score method for linkage analysis, we found the highest total lod score of 3.98 at a recombination fraction of 13%, suggesting the existence of a diabetic locus loosely linked to the HLA in these families; however, these results may have been influenced by the association between the HLA and IDDM (2,9), as discussed below. Conversely, the same method applied to the families published by Rubinstein et al (10), reportedly ascertained at random, showed a lod score of 0.88, thus failing to indicate linkage between the HLA and IDDM (9).…”

“…Assuming this genetic mode, when using the lod (the logarithm of odds) score method for linkage analysis, we found the highest total lod score of 3.98 at a recombination fraction of 13%, suggesting the existence of a diabetic locus loosely linked to the HLA in these families; however, these results may have been influenced by the association between the HLA and IDDM (2,9), as discussed below. Conversely, the same method applied to the families published by Rubinstein et al (10), reportedly ascertained at random, showed a lod score of 0.88, thus failing to indicate linkage between the HLA and IDDM (9). This suggests that our findings of linkage imay be specific for the specially selected families studied by Us (1,9), and may not be applicable to famnilies ascertained at randomn or according to other criteria.…”

“…Although a less efficient method to detect linkage in the MG f:amilies, the affected sib/sib pair concordance analysis was also performed to compare the results with those obtained by similar analysis in the MS fainilies. (1,9). The latter were ascertainied to maximl-ize the likelihood of dealinig with a genetically homnogeneous form (or forms) of autosomiial recessive IDDM.…”