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Similarly, the frequency of A*03 positivity was significantly increased in Alabama hemochromatosis probands diagnosed before the discovery of HFE [ 21 ] . These observations are consistent with and extend the findings of 21 previously reported case-controlled studies from thirteen countries which demonstrate the significantly increased prevalence of A*03 in persons with hemochromatosis [ 16 ] . The alleles B*07 and B*14 were also more common in the present Alabama probands and in Alabama probands diagnosed before discovery of HFE than in corresponding control subjects [ 21 ] . The present analysis demonstrates that this is attributable largely to the association of B*07 and B*14 with A*03, consistent with observations in persons with hemochromatosis patients from many locations, including Ireland [ 6 ] , Brittany [ 2 32 33 34 ] , Denmark [ 7 8 ] , Sweden [ 9 35 36 ] , Germany [ 10 11 37 38 ] , Portugal [ 30 39 ] , Italy [ 2 40 ] , and Utah [ 20 ] .
This disorder is typically associated with homozygosity for the C282Y mutation of the HFE gene (exon 2, nt 845 G→A) on Ch6p [ 1 ] . C282Y lies within an ancestral haplotype which includes the human leukocyte antigen (HLA) haplotype A*03-B*07 [ 2 3 4 5 ] . The ancestral haplotype is the predominant hemochromatosis-associated haplotype in many northwestern European countries, including Ireland [ 6 ] , Brittany [ 2 ] , Denmark [ 7 8 ] , Sweden [ 9 ] , and Germany [ 10 11 ] . This is attributed to the origin of the C282Y mutation on an A*03-B*07 haplotype in northwestern Europe and its early dissemination by Vikings [ 3 12 ] . Modification of the ancestral chromosome by recombination and admixture as a result of geographic migration explains the occurrence of chromosomes bearing C282Y in association with different HLA haplotypes [ 2 4 8 13 14 15 16 ] . Thus some non-ancestral haplotypes also occur with significantly increased frequencies in hemochromatosis patients in various countries in Europe and in descendants of Europeans [ 5 16 ] .
We compared the present results with data in a previously published tabulation of A and B haplotypes which occurred with significantly greater frequency in hemochromatosis patients than in corresponding control patients; data were available from Germany, Denmark, Sweden, Brittany, Portugal, Italy, Australia, and Utah (Table 5) [ Additional file 3] [ 16 ] [ 31 ] . Frequencies of the A*03-B*07 haplotype were increased in all hemochromatosis patient groups.
In your letter, you mentioned Navajo and Breton (the Celtic language of Brittany); coincidentally, this morning I got a letter from a colleague who has published an extensive dictionary of Hopi and is working with educators to help Hopi children learn their ancestral language.
The frequencies of the A*03-B*14 haplotype were significantly increased in persons with hemochromatosis in Brittany, Sweden, Utah, and Alabama (Table 5) [ Additional file 3] [ 31 ] . A significantly increased absolute frequency of the haplotype A*03-B*35 occurred in Alabama probands and in hemochromatosis patients in Italy [ 29 ] . A significantly increased frequency of the haplotype A*03-B*15 was observed in the present Alabama hemochromatosis probands; a relative increase in this haplotype was detected in hemochromatosis cohorts in Brittany and Utah [ 2 20 ] . A significantly increased frequency of the haplotype A*03-B*44 was observed in the present Alabama hemochromatosis probands, whereas a relative increase in this haplotype was reported in hemochromatosis cohorts in Sweden, Brittany, and Utah only after "correction" of the data for the preponderance of other haplotypes (Table 5) [ Additional file 3] [ 31 ] . The increased frequencies of the A*01-B*60, A*02-B*39, A*02-B*62, A*03-B*13, A*03-B*27, A*03-B*47, and A*03-B*57 haplotypes observed in Alabama probands in the present study were not reported in persons with hemochromatosis in the seven other countries for which data were available (Table 5) [ Additional file 3] [ 31 ] .
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