homologous to human hla dq. several autoimmune diseases that occur in humans that are mediated by dq also can be induced in mice and are mediated through ia. myasthenia gravis is an example of one such disease. linking specific sites on autoantigens is more difficult in humans due to the complex variation of heterologous humans, but subtle differences in t-cell stimulation associated with dq-types has been observed. these studies indicate that potentially a small change or increase in the presentation of a potential self-antigen can result in autoimmunity. this may explain why there is often linkage to dr or dq, but the linkage is often weak. regional evolution hla dq- subunit alleles, mature chains, contact variants knownhla-dqpotential locus:a1b1combinations alleles 3378 2475 subunit:αβ isoforms mature chains 2458 1392 contact variants* ~940 360 caucasian (usa) contact variants (cv) 712 84 cv-haplotypes 30 *subunits vary within 9â of peptide in dq2.5 or dq8 many hla dq were under positive selection of 10,000s potentially 100,000s of years in some regions. as people moved they have tended to lose haplotypes and in the process lose allelic diversity. on the other hand, on arrival at new distal locations, selection would offer unknown selective forces that would have initially favored diversity in arrivals. by an unknown process, rapid evolution occurs, as has been seen in south americas indigenous population (parham and ohta, 1996, watkins 1995), and new alleles rapidly appear. this process may be of immediate benefit of being positively selective in that new environment, but these new alleles might also be 'sloppy' in a selective perspective, having side effects if selection changed. the table to the left demonstrates how absolute diversity at the global level translates into relative diversity at the regional level. - heterozygous dq combinations and disease dq2.5 dq8 dq2.5/8 sweden 15.9 18.7 5.9 jalisco 11.4 22.8 5.2 england 12.4 16.8 4.2 kazakh 13.1 11 2.9 uygur 12.6 11.4 2.9 finland 9 15.7 2.8 poland 10.7 9.9 2.1 dq2.5/dq8 heterozygotes the distribution of this phenotype is largely the result of admixtures between peoples of eastern or central asian origin and peoples of western or central asian origin. the highest frequencies, by random mating, are expected in sweden, but pockets of high levels also occur in mexico, and a larger range risk exists in central asia. diseases that appear to be increased in heterozygotes are celiac disease and type 1 diabetes. new evidence is showing an increased risk for late onset type 1 diabetes in heterozygotes (which includes ambiguous type 1/type 2 diabetes). 95% of celiac disease patients are positive for dq2 or dq8.