However, due to heavy linkage disequilibrium between these alleles, most of the times they will probably be in cis. This proportion can be estimated based upon the presence of TNFa1b5 in DR3-negative individuals: 8 carriers out of 109 DR3-negative T1D patients, and 13 carriers out of 376 DR3-negative healthy controls. This evidence concerns the gene TNFRSF25 and type 1 diabetes mellitus.