{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T23:41:31Z","timestamp":1698709291996},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,6,28]],"date-time":"2008-06-28T00:00:00Z","timestamp":1214611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2008,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Background:\u2002<\/jats:bold> The hemochromatosis mutation, C282Y of the HFE gene, seems to have originated from a single event which once occurred in a person living in the north west of Europe carrying human leukocyte antigen (HLA)\u2010A3\u2010B7. In descendants of this ancestor also other haplotypes appear probably caused by local recombinations and founder effects. The background of these associations is unknown. Isolated river valley populations may be fruitful for the mapping of genetic disorders such as hemochromatosis. In this study, we try to test this hypothesis in a study from central Sweden where the haplotyope A1\u2010B8 was common.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> HLA haplotypes and HFE mutations were studied in hemochromatosis patients with present or past parental origin in a sparsely populated (1\/km<jats:sup>2<\/jats:sup>) rural district (<jats:italic>n<\/jats:italic>\u2003=\u20038366 in the year of 2005), in central Sweden. Pedigrees were constructed from the Swedish church book registry. Extended haplotypes were studied to evaluate origin of recombinations.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> There were 87 original probands, 36 females and 51 males identified during 30\u2003yr, of whom 86% carried C282Y\/C282Y and 14% C282Y\/H63D. Of 32 different HLA haplotypes A1\u2010B8 was the most common (34%), followed by A3\u2010B7 (16%), both in strong linkage disequilibrium with controls, (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.001). Twenty\u2010nine different families with A1\u2010B8 had a common founder origin 15 generations ago in small bottleneck populations of the late 16th century. A second A1\u2010B8 founder born 1655 was of Norwegian origin. Most of the A3 carriers (<jats:italic>n<\/jats:italic>\u2003=\u200326) had a common founder origin 16 generations ago in an even smaller nearby river valley. A fourth founder family carrying HLA\u2010A2 seems to have originated from a recombination along the descendant lines from the A3 ancestor supported by extended haplotype studies. A1\u2010haplotypes with alleles at the B locus different from B8 had a similar recombination origin as HLA\u2010A2 alleles and a common founder origin 11 generations ago. The intergenerational time interval averaged 35.5\u2003\u00b1\u20037.9\u2003yr in men and 31.9\u2003\u00b1\u20035.9 in females.<\/jats:p><jats:p><jats:bold>Conclusions:\u2002<\/jats:bold> River valley populations may contain HLA haplotypes reflecting their demographic history. This study has demonstrated that the resistance against recombinations between HLA\u2010A and HFE make HLA haplotypes excellent markers for population movements. Founder effects and genetic drift from bottleneck populations (surviving the plague?) may explain the commonness of the mutation in central Scandinavia. The intergenerational time difference &gt;30\u2003yr was greater than expected and means that the age of the original mutation may be underestimated.<\/jats:p>","DOI":"10.1111\/j.1600-0609.2008.01078.x","type":"journal-article","created":{"date-parts":[[2008,3,19]],"date-time":"2008-03-19T13:50:54Z","timestamp":1205934654000},"page":"36-46","source":"Crossref","is-referenced-by-count":11,"title":["HLA haplotype map of river valley populations with hemochromatosis traced through five centuries in Central Sweden"],"prefix":"10.1111","volume":"81","author":[{"given":"K. 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