The C282Y mutation may have been positively selected as it mitigates the infertility of celiac disease

Whittington, Chris

doi:10.1016/j.mehy.2005.10.023

Cited by 6 publications

(7 citation statements)

References 15 publications

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“…Hemochromatosis, known as the "Celtic" disease (44), is a variably penetrant recessive disorder, potentially fatal, due to excessive retention of dietary iron. It has been suggested that the high frequencies of both C282Y and H63D are due to heterozygote advantage related to nutritional advantage in Neolithic iron-poor diets (52), mitigation of celiac disease (53), and increased resistance to parasitic infection (54). To our knowledge, our data provide the first evidence for known Mendelian disease alleles in ancient genomes and mark the associations of both hemochromatosis alleles with the island of Ireland as ancient.…”

Section: Hungarian Neolithic -Ne1mentioning

confidence: 51%

Neolithic and Bronze Age migration to Ireland and establishment of the insular Atlantic genome

Cassidy

Martiniano

Murphy³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

222

177

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The Neolithic and Bronze Age transitions were profound cultural shifts catalyzed in parts of Europe by migrations, first of early farmers from the Near East and then Bronze Age herders from the Pontic Steppe. However, a decades-long, unresolved controversy is whether population change or cultural adoption occurred at the Atlantic edge, within the British Isles. We address this issue by using the first whole genome data from prehistoric Irish individuals. A Neolithic woman (3343–3020 cal BC) from a megalithic burial (10.3× coverage) possessed a genome of predominantly Near Eastern origin. She had some hunter–gatherer ancestry but belonged to a population of large effective size, suggesting a substantial influx of early farmers to the island. Three Bronze Age individuals from Rathlin Island (2026–1534 cal BC), including one high coverage (10.5×) genome, showed substantial Steppe genetic heritage indicating that the European population upheavals of the third millennium manifested all of the way from southern Siberia to the western ocean. This turnover invites the possibility of accompanying introduction of Indo-European, perhaps early Celtic, language. Irish Bronze Age haplotypic similarity is strongest within modern Irish, Scottish, and Welsh populations, and several important genetic variants that today show maximal or very high frequencies in Ireland appear at this horizon. These include those coding for lactase persistence, blue eye color, Y chromosome R1b haplotypes, and the hemochromatosis C282Y allele; to our knowledge, the first detection of a known Mendelian disease variant in prehistory. These findings together suggest the establishment of central attributes of the Irish genome 4,000 y ago.

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Section: Hungarian Neolithic -Ne1mentioning

confidence: 51%

Neolithic and Bronze Age migration to Ireland and establishment of the insular Atlantic genome

Cassidy

Martiniano

Murphy³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

222

177

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“…Aside from celiac disease and gluten sensitivities, wheaten bread contains phytates, iron chelators that can interfere with iron absorption in the digestive tract (McCullough et al, 2015). The collective effect of the adoption of wheaten bread was an elevated risk for iron‐deficiency anemia and further selection for C282Y's iron‐conserving benefit, particularly among adult females and children who, due to the iron‐related demands of menstruation and pregnancy, and growth and development, possess higher bodily iron needs to be met and satisfied from their diets (Cao & O'Brien, 2013; Lönnerdal, 2017; Whittington, 2006). Such age‐related vulnerabilities to iron deficiency anemia continue to be observed in contemporary developing countries, among children facing reduced iron bioavailability in low meat, high legume and cereal‐based diets (Skolmowska & Glabska, 2019; Zimmermann et al, 2005), and among infants weaned onto cereals containing potent phytic acid at precisely the time their bodily demands to fuel healthy growth and development are high (Hurrell et al, 2003).…”

Section: C282y In Ireland: Diet and Post‐famine Stressorsmentioning

confidence: 99%

“…Meanwhile, earlier in the life course the tendency towards iron accumulation and storage may have multiple protective benefits depending on context and stressors (Whittington, 2006).…”

mentioning

confidence: 99%

Famine, tea, and bread in Ireland: C282Y and modern human microevolution

Burke

Duffy

2022

American Journal of Biological Anthropology

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The HFE gene variant allele C282Y connected with hereditary hemochromatosis occurs at a frequency of about 10%–11% in Ireland, the highest known frequency in the modern global population. In this synthesis, we draw together an interdisciplinary literature to offer an agriculturally‐grounded, biocultural example of modern human adaptation and microevolution that addresses Ireland's comparatively high C282Y frequency. We argue that changing subsistence‐, diet‐, and nutrition‐related stressors framed under colonial governance played a role shaping the biology of Ireland's population historically, maintaining the C282Y variant. A population accustomed to challenges of poverty and difficult living conditions, the Irish fell under the influence of massive ecological stress with the fungus (Phytophthora infestans), the failed potato crops, and the Great Famine of 1845–52. From there, in the post‐Famine era, diet and nutrition altered further as the potato was exchanged for gluten‐rich wheaten bread and stewed black tea. With risks for iron deficiency anemia heightened by the cultural construction of diet and niche, an adaptive iron‐conserving advantage continued to be offered by the C282Y allele, influencing survival into the post‐Famine era. More recently, however, C282Y has been reframed as a potential risk in the context of contemporary, iron fortified diets.

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“…On the other hand, HH may be present in subjects negative to HFE gene mutations, particularly in geographic area different from northern Europe [20]. The interesting correlations between hemochromatosis and celiac disease: a first study demonstrated that occult celiac disease prevents penetrance of hemochromatosis [21]; later, it was evidenced that the C282Y mutation of HFE gene may mitigate the severity of celiac disease [22], and finally a large case-control study concluded that hemochromatosis predispose to celiac disease [23]. …”

Section: Hereditary Hemochromatosismentioning

confidence: 99%

An Update on Laboratory Diagnosis of Liver Inherited Diseases

Zarrilli

Elce

Scorza

et al. 2013

BioMed Research International

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Liver inherited diseases are a group of genetically determined clinical entities that appear with an early chronic liver involvement. They include Wilson's disease (hepatolenticular degeneration), hereditary hemochromatosis, and alpha-1-antitrypsin deficiency. In addition, cystic fibrosis, although it is not specifically a liver disease, may cause a severe liver involvement in a significant percentage of cases. For all these pathologies, the disease gene is known, and molecular analysis may contribute to the unequivocal diagnosis. This approach could avoid the patient invasive procedures and limit complications associated with a delay in diagnosis. We review liver inherited diseases on the basis of the genetic defect, focusing on the contribution of molecular analysis in the multistep diagnostic workup.

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The C282Y mutation may have been positively selected as it mitigates the infertility of celiac disease

Cited by 6 publications

References 15 publications

Neolithic and Bronze Age migration to Ireland and establishment of the insular Atlantic genome

Neolithic and Bronze Age migration to Ireland and establishment of the insular Atlantic genome

Famine, tea, and bread in Ireland: C282Y and modern human microevolution

An Update on Laboratory Diagnosis of Liver Inherited Diseases

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