Frequency Analysis and Allele Map in Favor of the Celtic Origin of the C282Y Mutation of Hemochromatosis
After the main hereditary hemochromatosis mutation C282Y in the HFE gene was described, we report here the C282Y frequencies for various European populations. The aim of this meta-analysis is to compile the Y allele frequencies of the C282Y mutation for 53 European populations, representing a total of 9265 unrelated people representing control samples. The most elevated values are observed in residual Celtic populations in Ireland, in the United Kingdom, and in France, in accordance with the initial hypothesis of Simon et al. (Prog. Med. Genet. 4, 135–168, 1980) concerning a Celtic origin of the hereditary hemochromatosis mutation.
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Celtic Origin of the C282Y Mutation of Hemochromatosis
The C282Y mutation in the HFE gene is the main mutation causing hemochromatosis, and C282Y frequencies have been reported for various European populations. The aim of this review is to compile the Y allele frequencies of the C282Y mutation for twenty European populations. The most elevated value (6.88%) is observed in residual Celtic populations in UK and France, in accordance to the hypothesis of Simon et al. concerning a Celtic origin of the hereditary hemochromatosis mutation.
PDF file
The Hemochromatosis 845 G
A and 187 CG Mutations: Prevalence in Non-Caucasian Populations
Hemochromatosis, the inherited disorder of iron metabolism, leads, if untreated, to progressive iron overload and premature death. The hemochromatosis gene, HFE, recently has been identified, and characterization of this gene has shown that it contains two mutations that result in amino acid substitutions
cDNA nucleotides 845 GA (C282Y) and 187 CG (H63D). Although hemochromatosis is common in Caucasians, affecting 1/300 individuals of northern European origin, it has not been recognized in other populations. The present study used PCR and restriction-enzyme digestion to analyze the frequency of the 845 GA and 187 CG mutations in HLA-typed samples from non-Caucasian populations, comprising Australian Aboriginal, Chinese, and Pacific Islanders. Results showed that the 845 GA mutation was present in these populations (allele frequency 0.32%), and, furthermore, it was always seen in conjunction with HLA haplotypes common in Caucasians, suggesting that 845 GA may have been introduced into these populations by Caucasian admixture. 187 CG was present at an allele frequency of 2.68% in the two populations analyzed (Australian Aboriginal and Chinese). In the Australian Aboriginal samples, 187 CG was found to be associated with HLA haplotypes common in Caucasians, suggesting that it was introduced by recent admixture. In the Chinese samples analyzed, 187 CG was present in association with a wide variety of HLA haplotypes, showing this mutation to be widespread and likely to predate the more genetically restricted 845 GA mutation.
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Maternal legacy of Bretons reveals common features with the extant Scottish mtDNA
Brittany is a peninsula located in western France, between the English Channel and the Atlantic Ocean. This country is peopled by a Celtic minority of 4.5 millions inhabitants, some of them, especially in western Brittany, are still speaking Breton, a Celtic language closely related to the Welsh. Bretons came from Great Britain at the end of the Roman Empire, during the 5th and 6th centuries. Most of them are told to be arrived from Cornwall and from Wales. This migration was important enough to let in Brittany a strong Celtic print in the culture and in the language. We are studying the genetic history of the Bretons. This first work, presented here, has been performed on 121 Breton mtDNAs of Nord-Finistere (Area of Plouescat, Brignogan, Roscoff). We analyse specific features of this Breton population compared to an average French one and its links to the Celtic populations over the channel. Quite interestingly, several unique exact matches between the studied here Breton maternal lineages are in fact between them and those in the Scottish people.
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Linkage disequilibrium between the four most common cystic fibrosis mutations and microsatellite haplotypes in the Celtic population of Brittany
Microsatellite haplotypes were determined for 117 chromosomes carrying the four most frequent mutations in the cystic fibrosis (CF) gene identified in the Breton population of Celtic origin, as well as for 83 normal chromosomes (noncarriers of a CF mutation). Each of the three non-delta F508 mutations was associated with a single haplotype: 1078deIT with 16-31-13, G55ID with 16-7-17, and W846X with 16-32-13. Although these results suggest identity-by-descent for each mutation, recurrent mutations, although unlikely, could not be completely ruled out. The four most frequent haplotypes on normal chromosomes and the three most frequent haplotypes on delta F508 chromosomes are the same as those found in Ireland, Spain, and Italy. This suggests that some haplotypes, associated or not with the delta F508 mutation, were present in an ancestral population from which all four populations descended.
PDF file
After the main hereditary hemochromatosis mutation C282Y in the HFE gene was described, we report here the C282Y frequencies for various European populations. The aim of this meta-analysis is to compile the Y allele frequencies of the C282Y mutation for 53 European populations, representing a total of 9265 unrelated people representing control samples. The most elevated values are observed in residual Celtic populations in Ireland, in the United Kingdom, and in France, in accordance with the initial hypothesis of Simon et al. (Prog. Med. Genet. 4, 135–168, 1980) concerning a Celtic origin of the hereditary hemochromatosis mutation.
PDF file
Celtic Origin of the C282Y Mutation of Hemochromatosis
The C282Y mutation in the HFE gene is the main mutation causing hemochromatosis, and C282Y frequencies have been reported for various European populations. The aim of this review is to compile the Y allele frequencies of the C282Y mutation for twenty European populations. The most elevated value (6.88%) is observed in residual Celtic populations in UK and France, in accordance to the hypothesis of Simon et al. concerning a Celtic origin of the hereditary hemochromatosis mutation.
PDF file
The Hemochromatosis 845 G
A and 187 CG Mutations: Prevalence in Non-Caucasian Populations
Hemochromatosis, the inherited disorder of iron metabolism, leads, if untreated, to progressive iron overload and premature death. The hemochromatosis gene, HFE, recently has been identified, and characterization of this gene has shown that it contains two mutations that result in amino acid substitutions
cDNA nucleotides 845 GA (C282Y) and 187 CG (H63D). Although hemochromatosis is common in Caucasians, affecting 1/300 individuals of northern European origin, it has not been recognized in other populations. The present study used PCR and restriction-enzyme digestion to analyze the frequency of the 845 GA and 187 CG mutations in HLA-typed samples from non-Caucasian populations, comprising Australian Aboriginal, Chinese, and Pacific Islanders. Results showed that the 845 GA mutation was present in these populations (allele frequency 0.32%), and, furthermore, it was always seen in conjunction with HLA haplotypes common in Caucasians, suggesting that 845 GA may have been introduced into these populations by Caucasian admixture. 187 CG was present at an allele frequency of 2.68% in the two populations analyzed (Australian Aboriginal and Chinese). In the Australian Aboriginal samples, 187 CG was found to be associated with HLA haplotypes common in Caucasians, suggesting that it was introduced by recent admixture. In the Chinese samples analyzed, 187 CG was present in association with a wide variety of HLA haplotypes, showing this mutation to be widespread and likely to predate the more genetically restricted 845 GA mutation.
PDF file
Maternal legacy of Bretons reveals common features with the extant Scottish mtDNA
Brittany is a peninsula located in western France, between the English Channel and the Atlantic Ocean. This country is peopled by a Celtic minority of 4.5 millions inhabitants, some of them, especially in western Brittany, are still speaking Breton, a Celtic language closely related to the Welsh. Bretons came from Great Britain at the end of the Roman Empire, during the 5th and 6th centuries. Most of them are told to be arrived from Cornwall and from Wales. This migration was important enough to let in Brittany a strong Celtic print in the culture and in the language. We are studying the genetic history of the Bretons. This first work, presented here, has been performed on 121 Breton mtDNAs of Nord-Finistere (Area of Plouescat, Brignogan, Roscoff). We analyse specific features of this Breton population compared to an average French one and its links to the Celtic populations over the channel. Quite interestingly, several unique exact matches between the studied here Breton maternal lineages are in fact between them and those in the Scottish people.
PDF file
Linkage disequilibrium between the four most common cystic fibrosis mutations and microsatellite haplotypes in the Celtic population of Brittany
Microsatellite haplotypes were determined for 117 chromosomes carrying the four most frequent mutations in the cystic fibrosis (CF) gene identified in the Breton population of Celtic origin, as well as for 83 normal chromosomes (noncarriers of a CF mutation). Each of the three non-delta F508 mutations was associated with a single haplotype: 1078deIT with 16-31-13, G55ID with 16-7-17, and W846X with 16-32-13. Although these results suggest identity-by-descent for each mutation, recurrent mutations, although unlikely, could not be completely ruled out. The four most frequent haplotypes on normal chromosomes and the three most frequent haplotypes on delta F508 chromosomes are the same as those found in Ireland, Spain, and Italy. This suggests that some haplotypes, associated or not with the delta F508 mutation, were present in an ancestral population from which all four populations descended.
PDF file
