PMID- 18363869
OWN - NLM
STAT- MEDLINE
DCOM- 20080729
LR  - 20220311
IS  - 1600-0609 (Electronic)
IS  - 0902-4441 (Linking)
VI  - 81
IP  - 1
DP  - 2008 Jul
TI  - HLA haplotype map of river valley populations with hemochromatosis traced through 
      five centuries in Central Sweden.
PG  - 36-46
LID - 10.1111/j.1600-0609.2008.01078.x [doi]
AB  - BACKGROUND: 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)-A3-B7. 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-B8 was common. 
      METHODS: HLA haplotypes and HFE mutations were studied in hemochromatosis 
      patients with present or past parental origin in a sparsely populated (1/km(2)) 
      rural district (n = 8366 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. RESULTS: There were 87 original 
      probands, 36 females and 51 males identified during 30 yr, of whom 86% carried 
      C282Y/C282Y and 14% C282Y/H63D. Of 32 different HLA haplotypes A1-B8 was the most 
      common (34%), followed by A3-B7 (16%), both in strong linkage disequilibrium with 
      controls, (P < 0.001). Twenty-nine different families with A1-B8 had a common 
      founder origin 15 generations ago in small bottleneck populations of the late 
      16th century. A second A1-B8 founder born 1655 was of Norwegian origin. Most of 
      the A3 carriers (n = 26) had a common founder origin 16 generations ago in an 
      even smaller nearby river valley. A fourth founder family carrying HLA-A2 seems 
      to have originated from a recombination along the descendant lines from the A3 
      ancestor supported by extended haplotype studies. A1-haplotypes with alleles at 
      the B locus different from B8 had a similar recombination origin as HLA-A2 
      alleles and a common founder origin 11 generations ago. The intergenerational 
      time interval averaged 35.5 +/- 7.9 yr in men and 31.9 +/- 5.9 in females. 
      CONCLUSIONS: River valley populations may contain HLA haplotypes reflecting their 
      demographic history. This study has demonstrated that the resistance against 
      recombinations between HLA-A 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 >30 yr was greater 
      than expected and means that the age of the original mutation may be 
      underestimated.
FAU - Olsson, K Sigvard
AU  - Olsson KS
AD  - Department of Medicine, Sahlgren's University Hospital, Goteborg, Sweden. 
      sigvard.olsson@medic.gu.se
FAU - Ritter, Bernd
AU  - Ritter B
FAU - Hansson, Norbeth
AU  - Hansson N
FAU - Chowdhury, Ruma R
AU  - Chowdhury RR
LA  - eng
PT  - Historical Article
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080319
PL  - England
TA  - Eur J Haematol
JT  - European journal of haematology
JID - 8703985
RN  - 0 (HFE protein, human)
RN  - 0 (HLA Antigens)
RN  - 0 (Hemochromatosis Protein)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Membrane Proteins)
SB  - IM
MH  - Female
MH  - *Founder Effect
MH  - Genetics, Population
MH  - *HLA Antigens
MH  - *Haplotypes
MH  - Hemochromatosis/epidemiology/*genetics/history
MH  - Hemochromatosis Protein
MH  - Histocompatibility Antigens Class I/*genetics
MH  - History, 17th Century
MH  - History, 18th Century
MH  - History, 19th Century
MH  - History, 20th Century
MH  - History, 21st Century
MH  - Humans
MH  - Male
MH  - Membrane Proteins/*genetics
MH  - *Pedigree
MH  - Point Mutation
MH  - Rivers
MH  - Sweden
EDAT- 2008/03/28 09:00
MHDA- 2008/07/30 09:00
CRDT- 2008/03/28 09:00
PHST- 2008/03/28 09:00 [pubmed]
PHST- 2008/07/30 09:00 [medline]
PHST- 2008/03/28 09:00 [entrez]
AID - EJH1078 [pii]
AID - 10.1111/j.1600-0609.2008.01078.x [doi]
PST - ppublish
SO  - Eur J Haematol. 2008 Jul;81(1):36-46. doi: 10.1111/j.1600-0609.2008.01078.x. Epub 
      2008 Mar 19.