Global prevalence of putative haemochromatosis mutations.

Merryweather‐Clarke, Alison T.; Pointon, Jennifer J.; Shearman, Jeremy D.; Robson, Kathryn

doi:10.1136/jmg.34.4.275

Cited by 722 publications

(492 citation statements)

References 31 publications

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“…First, published studies on the frequency of the C282Y allele from The Faroe Islands (Merryweather‐Clarke et al, 1998; Milman et al, 2005) and Iceland (Merryweather‐Clarke et al, 1997, 1999) are not included in our study. Current archaeological evidence suggests that the Faroe Islands may have been sparsely occupied before the Vikings as early as the 4th century ACE (Church et al, 2013) but the evidence is not associated with Neolithic occupation.…”

Section: Methodsmentioning

confidence: 99%

“…Since our research question concerns the adaptive significance of the C282Y allele among European Neolithic farmers, these locations are also excluded from our analysis. Third, we are not including studies on the Basque (Merryweather‐Clarke et al, 1997; Baiget et al, 1998; Mercier et al, 1998), Roma (Szakony et al, 1999; Gabriková et al, 2012) or Saami (Beckman et al, 2001) as they are considered separate ethnic groups and do not represent the national population.…”

Section: Methodsmentioning

confidence: 99%

“…The C282Y allele is found predominantly among European populations reaching polymorphic levels in the northwest (Merryweather‐Clarke et al, 2000, 1997). Highest frequencies are found in Ireland (mean 10.1%) and prevalence declines to near 0% in southeast Europe (Fairbanks, 2000; Olsson et al, 2011).…”

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confidence: 99%

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The evolutionary adaptation of the C282Y mutation to culture and climate during the European Neolithic

Heath

Axton

McCullough

et al. 2016

American J Phys Anthropol

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ObjectivesThe C282Y allele is the major cause of hemochromatosis as a result of excessive iron absorption. The mutation arose in continental Europe no earlier than 6,000 years ago, coinciding with the arrival of the Neolithic agricultural revolution. Here we hypothesize that this new Neolithic diet, which originated in the sunny warm and dry climates of the Middle East, was carried by migrating farmers into the chilly and damp environments of Europe where iron is a critical micronutrient for effective thermoregulation. We argue that the C282Y allele was an adaptation to this novel environment.Materials and MethodsTo address our hypothesis, we compiled C282Y allele frequencies, known Neolithic sites in Europe and climatic data on temperature and rainfall for statistical analysis.ResultsOur findings indicate that the geographic cline for C282Y frequency in Europe increases as average temperatures decrease below 16°C, a critical threshold for thermoregulation, with rainy days intensifying the trend.DiscussionThe results indicate that the deleterious C282Y allele, responsible for most cases of hemochromatosis, may have evolved as a selective advantage to culture and climate during the European Neolithic. Am J Phys Anthropol 160:86–101, 2016. © 2016 The Authors American Journal of Physical Anthropology Published by Wiley Periodicals, Inc.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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The evolutionary adaptation of the C282Y mutation to culture and climate during the European Neolithic

Heath

Axton

McCullough

et al. 2016

American J Phys Anthropol

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“…It also has a much wider geographical distribution, being present at varying allele frequencies in most of the world's populations. 6 p.His63Asp is generally not considered to be a pathogenic mutation because the majority of people who are homozygous show no evidence of iron overload. Individuals who are compound heterozygous for p.Cys282Tyr and p.His63Asp can develop iron overload, and this variant is enriched among individuals with a diagnosis of HH.…”

Section: Introductionmentioning

confidence: 99%

The global prevalence of HFE and non-HFE hemochromatosis estimated from analysis of next-generation sequencing data

Wallace

Subramaniam

2016

Genetics in Medicine

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Purpose:The prevalence of HFE-related hereditary hemochromatosis (HH) among European populations has been well studied. There are no prevalence data for atypical forms of HH caused by mutations in HFE2, HAMP, TFR2, or SLC40A1. The purpose of this study was to estimate the population prevalence of these non-HFE forms of HH.Methods: A list of HH pathogenic variants in publically available next-generation sequence (NGS) databases was compiled and allele frequencies were determined.Results: Of 161 variants previously associated with HH, 43 were represented among the NGS data sets; an additional 40 unreported functional variants also were identified. The predicted prevalence of HFE HH and the p.Cys282Tyr mutation closely matched previous estimates from similar populations. Of the non-HFE forms of iron overload, TFR2-, HFE2-, and HAMP-related forms are predicted to be rare, with pathogenic allele frequencies in the range of 0.00007 to 0.0005. Significantly, SLC40A1 variants that have been previously associated with autosomal-dominant ferroportin disease were identified in several populations (pathogenic allele frequency 0.0004), being most prevalent among Africans. Conclusion:We have, for the first time, estimated the population prevalence of non-HFE HH. This methodology could be applied to estimate the population prevalence of a wide variety of genetic disorders.

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“…Three HFE mutations have now been identified: C282Y, H63D and S65C. [9][10][11] C282Y, a G-to-A transition at nucleotide 845 (G845A) in exon 4 of the HFE gene, results in a cysteine-to-tyrosine substitution at position 282. H63D is a C-to-G transition at nucleotide 187 (C187G) in exon 2, causing a histidineto-aspartic acid substitution at amino acid 63.…”

Section: Introductionmentioning

confidence: 99%

An association study of HFE gene mutation with idiopathic male infertility in the Chinese Han population

Yu¹,

Wang²,

Xin³

et al. 2012

Asian J Androl

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Mutations in the haemochromatosis gene (HFE) influence iron status in the general population of Northern Europe, and excess iron is associated with the impairment of spermatogenesis. The aim of this study is to investigate the association between three mutations (C282Y, H63D and S65C) in the HFE gene with idiopathic male infertility in the Chinese Han population. Two groups of Chinese men were recruited: 444 infertile men (including 169 with idiopathic azoospermia) and 423 controls with proven fertility. The HFE gene was detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The experimental results demonstrated that no C282Y or S65C mutations were detected. Idiopathic male infertility was not significantly associated with heterozygous H63D mutation (odds ratio50.801, 95% confidence interval50.452-1.421, x 2 50.577, P50.448). The H63D mutation frequency did not correlate significantly with the serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone (T) levels in infertile men (P50.896, P50.404 and P50.05, respectively). Our data suggest that the HFE H63D mutation is not associated with idiopathic male reproductive dysfunction.

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Global prevalence of putative haemochromatosis mutations.

Cited by 722 publications

References 31 publications

The evolutionary adaptation of the C282Y mutation to culture and climate during the European Neolithic

The evolutionary adaptation of the C282Y mutation to culture and climate during the European Neolithic

The global prevalence of HFE and non-HFE hemochromatosis estimated from analysis of next-generation sequencing data

An association study of HFE gene mutation with idiopathic male infertility in the Chinese Han population

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