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Cited by 206Prion Diseases and Protein MisfoldingAmyloidosis: Diagnosis, Treatment, OutcomesAlzheimer's disease research and treatments

A Novel Protective Prion Protein Variant that Colocalizes with Kuru Exposure

Open access
Mead, Simon, Whitfield, Jerome, Poulter, Mark, Shah, Paresh, Uphill, James, Campbell, Tracy, Al-Dujaily, Huda, Hummerich, Holger +6 more·2009·New England Journal of Medicine
DOI 10.1056/nejmoa0809716
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Abstract

BACKGROUND: Kuru is a devastating epidemic prion disease that affected a highly restricted geographic area of the Papua New Guinea highlands; at its peak, it predominantly affected adult women and children of both sexes. Its incidence has steadily declined since the cessation of its route of transmission, endocannibalism. METHODS: We performed genetic and selected clinical and genealogic assessments of more than 3000 persons from Eastern Highland populations, including 709 who participated in cannibalistic mortuary feasts, 152 of whom subsequently died of kuru. RESULTS: Persons who were exposed to kuru and survived the epidemic in Papua New Guinea are predominantly heterozygotes at the known resistance factor at codon 129 of the prion protein gene (PRNP). We now report a novel PRNP variant--G127V--that was found exclusively in people who lived in the region in which kuru was prevalent and that was present in half of the otherwise susceptible women from the region of highest exposure who were homozygous for methionine at PRNP codon 129. Although this allele is common in the area with the highest incidence of kuru, it is not found in patients with kuru and in unexposed population groups worldwide. Genealogic analysis reveals a significantly lower incidence of kuru in pedigrees that harbor the protective allele than in geographically matched control families. CONCLUSIONS: The 127V polymorphism is an acquired prion disease resistance factor selected during the kuru epidemic, rather than a pathogenic mutation that could have triggered the kuru epidemic. Variants at codons 127 and 129 of PRNP demonstrate the population genetic response to an epidemic of prion disease and represent a powerful episode of recent selection in humans.

Integrity signals

Registry

Crossref · 10.1056/nejmoa0809716

Cites

29 of 29 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

3 of 16 cited sources checked · 1 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    A crystal structure of human PrP shows that interactions between neighboring PrP molecules are mediated by homotypic contacts between residues around position 129, leading to a four-strand intermolecular beta-sheet.

    “A crystal structure of human PrP shows that interactions between neighboring PrP molecules are mediated by homotypic contacts between residues around position 129, leading to a four-strand intermolecular β-sheet.28”
    Quote in the paperSubstantial claim1 of 1 sources checked
  • Premisecitation

    There are few examples of mutations that are causative of autosomal dominant neurodegenerative disease achieving the polymorphic frequency observed in the Purosa valley.

    “However, there are few examples of mutations that are causative of autosomal dominant neurodegenerative disease achieving the polymorphic frequency observed in the Purosa valley.29”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [29] source

      The paper identifies Huntington’s disease as an autosomal dominant neurodegenerative disease and describes the Venezuelan kindreds as the world’s largest genetically related HD community (opening section; Discussion, page unavailable). It therefore supplies an example of a large affected community, but it does not establish that such mutations rarely reach polymorphic frequency or compare their frequency with that in the Purosa valley. (LLM, conf=0.79)

      Experimental — accuracy not yet measured
  • Findingown data

    In the 546 persons from low-exposure zones, the codon 129 allele count did not differ significantly from that in the kuru region.

    “The codon 129 allele count did not differ significantly from that in the kuru region.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The exposure index based on participation in mortuary feasts is a valid measure of exposure to kuru.
  • Findingown data

    A novel PRNP variant G127V was found exclusively in people who lived in the region in which kuru was prevalent.

    “We now report a novel PRNP variant -G127V -that was found exclusively in people who lived in the region in which kuru was prevalent”
    Quote in the paperSubstantial claim
  • Findingown data

    Genealogic analysis reveals a significantly lower incidence of kuru in pedigrees that harbor the protective allele than in geographically matched control families.

    “Genealogic analysis reveals a significantly lower incidence of kuru in pedigrees that harbor the protective allele than in geographically matched control families.”
    Quote in the paperSubstantial claim
  • May combine two claims. 22
  • Classified as probably not a substantial claim. 10

  • May combine two claims.

    Interpretationcitation

    In the folded PrP C conformation, residue 127 lies in a small beta-sheet, so the higher beta-propensity of valine might increase PrP C stability.

    “In the folded PrP C conformation, which is the normal form of the protein, this residue lies in a small β-sheet, so the higher β-propensity of valine might increase PrP C stability.27”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [27] source

      The study description and the section on effects of mutations examine beta-sheet propensities and stability in CD2.d1, not PrP C. Searches for PrP C residue 127 and for valine's beta-sheet propensity found no passage addressing the claimed structure or proposed stability effect. Page numbers were not available in our copy. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    The G127V allele is common in the area with the highest incidence of kuru but is not found in patients with kuru or in unexposed population groups worldwide.

    “Although this allele is common in the area with the highest incidence of kuru, it is not found in patients with kuru and in unexposed population groups worldwide.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Both 129MM and 129VV were associated with young persons with kuru, as compared with 129MV, which was associated with elderly women in midlevel-exposure and high-exposure zones (P = 3.5×10 -8 and P = 0.001).

    “Both 129MM and 129VV were associated with young persons with kuru, as compared with 129MV, which was associated with elderly women in midlevel-exposure and high-exposure zones (P = 3.5×10 -8 and P = 0.001 for the comparison of the frequency of 129MM and 129VV, respectively, with the frequency of 129MV, by the chi-square test with 1 df).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    No deletions of the entire PRNP gene or PRNP promoter polymorphisms were detected.

    “We did not detect deletions of the entire gene or PRNP promoter polymorphisms.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Among patients with kuru younger than 20 years of age, 36 of 48 were homozygous for the PRNP open reading frame (127GG-129MM or 127GG-129VV), as compared with 36 of 125 elderly women (P = 3.4×10 -8) and 27 of 104 patients with kuru older than 20 years at onset (P = 1.2×10 -8).

    “or 127GG-129VV), as compared with 36 of 125 elderly women (P = 3.4×10 -8 by the two-tailed chisquare test) and 27 of 104 patients with kuru who were older than 20 years of age at the onset of the disease (P = 1.2×10 -8 by the two-tailed chisquare test).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The loss of Hardy-Weinberg equilibrium at codon 129 is not found in a stratum of slightly younger women born between 1950 and 1960, and was not detected in elderly men and unexposed elderly women.

    “The loss of Hardy-Weinberg equilibrium at codon 129 is not found in a stratum of slightly younger women born between 1950 and 1960, which was the last period in which the dead were consumed at mortuary feasts, and was not detected in elderly men and unexposed elderly women.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The entire population of both sexes born before 1960 (480 persons in midlevel-exposure and high-exposure villages) shows marked loss of Hardy-Weinberg equilibrium at codon 129 (P = 4.6×10 -4), but not at codon 127.

    “The entire population of both sexes born before 1960 (480 persons in midlevelexposure and high-exposure villages) shows marked loss of Hardy-Weinberg equilibrium at codon 129 (P = 4.6×10 -4 by an exact method with the use of the PLINK software program [http:// pngu.mgh.harvard.edu/~purcell/plink/],but not at codon 127”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Among persons born before 1960, 127V alleles were more likely to be found in otherwise susceptible 129MM homozygotes than in 129MV heterozygotes (P = 0.02), whereas 127V and 129M were in equilibrium in persons born after 1960.

    “Among persons born before 1960, 127V alleles were more likely to be found in otherwise susceptible 129MM homozygotes than in 129MV heterozygotes (P = 0.02), whereas 127V and 129M were in equilibrium in persons who were born after 1960.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    As assessed with the PHASE software for haplotyping, 25 of 51 127V chromosomes share an identical microsatellite haplotype across the region, and the same haplotype was found in only 1 of 69 127G chromosomes.

    “As assessed with the use of the PHASE software for haplotyping, 25 of 51 127V chromosomes share an identical microsatellite haplotype across the region (Fig. 4 in the Supplementary Appendix); the same haplotype was found in only 1 of 69 127G chromosomes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    Heterozygosity at PRNP codons 127 or 129, or both, is highest in the zone of high kuru exposure, resulting in Hardy-Weinberg disequilibrium.

    “Heterozygosity at 127 or 129, or both, is highest in the zone of high exposure, resulting in Hardy-Weinberg disequilibrium.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    When data are stratified according to age, sex, and exposure, the most striking deficit of codon 129 homozygosity is found in elderly women from midlevel-exposure and high-exposure zones, in whom there is a marked loss of Hardy-Weinberg equilibrium at codon 129, in contrast to persons in low-exposure or unexposed zones (P = 3.1×10 -5).

    “When these data are stratified according to age, sex, and exposure, the most striking deficit of codon 129 homozygosity is found in elderly women from midlevel-exposure and high-exposure zones, in whom there is a marked loss of Hardy-Weinberg equilibrium at codon 129 -in contrast to persons in low-exposure or unexposed zones (P = 3.1×10 -5 by an exact method with the use of PLINK) (Table 1 and Fig”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Although no 127VV homozygotes were observed in the elderly population, consistent with Hardy-Weinberg equilibrium, 127V alleles were not in equilibrium with codon 129 genotypes.

    “Although our failure to observe any 127VV homozygotes in the elderly population is consistent with Hardy-Weinberg equilibrium, 127V alleles were not in equilibrium with codon 129 genotypes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Only 1 of 36 parents from 127V genealogies was recorded as having died from kuru, whereas 33 of 218 parents were recorded as having died from kuru in matched 127G pedigrees (P = 0.04 by a two-tailed chi-square test).

    “Despite this, only 1 of 36 parents from 127V genealogies was recorded as having died from kuru, whereas 33 of 218 parents were recorded as having died from kuru in the matched 127G pedigrees (P = 0.04 by a two-tailed chi-square test).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Parents of the living 127V probands would have lived through the peak kuru epidemic.
    • Rests on an assumption: One parent of a 127V proband would be expected to be a 127V carrier.

  • May combine two claims.

    Findingown data

    In the entire sample of 480 persons born before 1960 in midlevel-exposure and high-exposure villages, relative fitness was 0.64 for 127GG-129MM and 0.74 for 127GG-129VV relative to the three heterozygous genotypic combinations; for codon 129 alone, relative fitness was 0.69 for 129MM and 0.74 for 129VV relative to the 129MV genotype.

    “In the entire sample of 480 persons born before 1960 in midlevel-exposure and high-exposure villages, ω = 0.64 for 127GG-129MM and ω = 0.74 for 127GG-129VV relative to the three heterozygous genotypic combinations; for codon 129 alone, ω = 0.69 for 129MM and ω = 0.74 for 129VV relative to the 129MV genotype.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The three heterozygous genotypic combinations (127GV-129MM, 127GV-129MV, and 127GG-129MV) are equally the most viable genotypes.
    • The authors state this as an assumption: For codon 129 alone, the 129MV genotype is the most viable.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingnone given

    At equilibrium frequency, 48% of elderly women would be expected to be homozygous for PRNP.

    “At equilibrium frequency, 48% of elderly women would be expected to be homozygous for PRNP.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The 127V polymorphism is an acquired prion disease resistance factor selected during the kuru epidemic, rather than a pathogenic mutation that could have triggered the kuru epidemic.

    “The 127V polymorphism is an acquired prion disease resistance factor selected during the kuru epidemic, rather than a pathogenic mutation that could have triggered the kuru epidemic.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Kuru is a prion disease that affected the Fore linguistic group of the Eastern Highlands Province of Papua New Guinea and provides major experience with epidemic prion disease in humans.

    “Kuru is a prion disease that had a dramatic impact on the Fore linguistic group of the Eastern Highlands Province of Papua New Guinea 1 and that provides our major experience with epidemic prion disease in humans.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisereasoning

    At its peak, kuru predominantly affected adult women and children of both sexes.

    “at its peak, it predominantly affected adult women and children of both sexes.”
    • Also stated in: § Abstract · plain
      “with the result that kuru at its peak predominantly affected women and children.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Male members of the Fore group older than 6 to 8 years of age participated little, if at all, in mortuary feasts.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Investigators who obtained genealogic information were unaware of the participants' genetic data.

    “The investigators who obtained genealogic information were unaware of the participants' genetic data.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Variants at codons 127 and 129 of PRNP demonstrate the population genetic response to an epidemic of prion disease and represent a powerful episode of recent selection in humans.

    “Variants at codons 127 and 129 of PRNP demonstrate the population genetic response to an epidemic of prion disease and represent a powerful episode of recent selection in humans.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Kuru incidence has steadily declined and disappeared from the younger Fore population since the cessation of endocannibalism in the late 1950s.

    “Its incidence has steadily declined since the cessation of its route of transmission, endocannibalism.”
    • Also stated in: § Abstract · plain
      “Kuru has progressively disappeared from the younger Fore population, consistent with the cessation of endocannibalism in the late 1950s.5”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] Alpers MP, 2005, Commun Dis Intell

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Population structure was assessed with the use of EIGENSTRAT software or the genomic control method.

    “Population structure was assessed with the use of EIGENSTRAT soft-ware 23 or the genomic control method.24”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [23] source
    • cites [24] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Kuru is associated with prolonged incubation periods that may exceed five decades.

    “Kuru is associated with prolonged incubation periods that may exceed five decades.3”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] source

  • May combine two claims.

    Interpretationown data

    A novel PRNP allele, codon 127V, discovered at the epicenter of kuru exposure, is associated with resistance to kuru in patients and pedigrees and is found at the highest frequency in otherwise susceptible 129MM elderly women.

    “In addition, we have discovered at the epicenter of kuru exposure a novel PRNP allele -codon 127Vthat is associated with resistance to kuru in patients and pedigrees and is found at the highest frequency in otherwise susceptible 129MM elderly women.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The new data provide evidence of a complex selection event in the Fore population at PRNP during the kuru epidemic, with balancing selection acting to maximize heterozygosity at codon 129, coincident with positive selection acting to increase 127V alleles on a 129M background.

    “Our new data thus provide evidence of a complex selection event in the Fore population at PRNP during the kuru epidemic, with balancing selection acting to maximize heterozygosity at codon 129, coincident with positive selection acting to increase 127V alleles on a 129M background.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    This is consistent with the increase in the incidence of kuru through the early 20th century that was reported by elderly members of the Fore society.

    “This is consistent with the increase in the incidence of kuru through the early 20th century that was reported by elderly members of the Fore society.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In an earlier work, the authors proposed the theory that kuru imposed balancing selection on the Fore, acting at codon 129 of PRNP, although at the time they had sampled only 30 elderly exposed women.

    “In an earlier work, we proposed the theory that kuru imposed balancing selection on the Fore, acting at codon 129 of PRNP, although at the time we had sampled only 30 elderly exposed women.12”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Because mean life expectancy in the kuru region was thought to be between 40 and 45 years, the possibility cannot be excluded that 127V is associated with a late-onset, low-penetrance, or recessive inherited prion disease that might have triggered the kuru epidemic.

    “Since the mean life expectancy in the kuru region was thought to be between 40 and 45 years, we cannot exclude the possibility that 127V is associated with a late-onset, low-penetrance, or recessive inherited prion disease that might indeed have triggered the kuru epidemic.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Mean life expectancy in the kuru region was between 40 and 45 years.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The inherited prion diseases caused by point mutations are generally poorly transmissible, and in some cases not transmissible, to experimental animals and are associated with a molecular type of the disease-associated prion protein (PrP Sc) that is distinct from that of sporadic Creutzfeldt-Jakob disease or kuru.

    “The inherited prion diseases caused by point mutations are generally poorly transmissible, and in some cases not transmissible, to experimental animals and are associated with a molecular type of the disease-associated prion protein (PrP Sc ) that is distinct from that of sporadic Creutzfeldt-Jakob disease or kuru.16”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] source
29 of 29

  • The paper relies on this without support.

    Kuru was transmitted from human to human through the Fore practice of consuming deceased relatives at mortuary feasts (endocannibalism).

    “It was the practice in the Fore society for kinship groups to consume deceased relatives at mortuary feasts, a practice that resulted in human-to-human prion transmission”

  • The paper relies on this without support.

    Male members of the Fore group older than 6 to 8 years of age participated little, if at all, in mortuary feasts.

    “male members of the Fore group who were older than 6 to 8 years of age participated little, if at all, in these feasts”

  • The paper relies on this without support.

    Kuru was restricted to the Fore linguistic groups and their immediate neighbors with whom they intermarried.

    “Kuru was restricted to the Fore linguistic groups and their immediate neighbors with whom they intermarried.”

  • The paper relies on this without support.

    The exposure index based on participation in mortuary feasts is a valid measure of exposure to kuru.

    “We stratified these samples according to the critical determinants of exposure to kuru on the basis of participation in mortuary feasts: sex, date of birth, and village of residence.”

  • The paper relies on this without support.

    G127V is located in a highly conserved and structured region of PrP.

    “which is located in a highly conserved and structured region of PrP.”

  • The paper relies on this without support.

    In traditional Fore society, boys older than approximately 7 years of age would no longer participate in the consumption of highly infectious material from mortuary feasts.

    “In traditional Fore society, boys older than approximately 7 years of age would no longer participate in the consumption of highly infectious material from mortuary feasts.”

  • The paper relies on this without support.

    Elderly women from the kuru region who survived to old age were resistant to kuru.

    “since there is an excess of 129MV in elderly women who were resistant to kuru”

  • The paper relies on this without support.

    Kuru was transmitted through the consumption of highly infectious material from mortuary feasts.

    “In traditional Fore society, boys older than approximately 7 years of age would no longer participate in the consumption of highly infectious material from mortuary feasts.”

  • The paper relies on this without support.

    Parents of the living 127V probands would have lived through the peak kuru epidemic.

    “Parents of the living 127V probands would have lived through the peak kuru epidemic.”

  • The paper relies on this without support.

    One parent of a 127V proband would be expected to be a 127V carrier.

    “Since one parent would be expected to be a 127V carrier”

  • The paper relies on this without support.

    Mean life expectancy in the kuru region was between 40 and 45 years.

    “Since the mean life expectancy in the kuru region was thought to be between 40 and 45 years”

  • The paper relies on this without support.

    Oral history that the first kuru patient was observed in the Keiagana linguistic group, northwest of the Fore region, is accurate.

    “oral history that recorded that the first kuru patient was observed in the Keiagana linguistic group, which is located to the northwest of the Fore region.”

  • The authors state this as an assumption.

    The three heterozygous genotypic combinations (127GV-129MM, 127GV-129MV, and 127GG-129MV) are equally the most viable genotypes.

    “with all heterozygous combinations (127GV-129MM, 127GV-129MV, and 127GG-129MV) considered as equally the most viable genotypes”

  • The authors state this as an assumption.

    For codon 129 alone, the 129MV genotype is the most viable.

    “or for codon 129 alone, with the 129MV genotype considered as the most viable.”

  • The paper relies on this without support.

    Estimates of the onset of the kuru epidemic based on recollections of elderly Fore group members are accurate.

    “estimates of the onset of the kuru epidemic that are based on recollections of the elderly members of the Fore group”
15 of 15

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The loss of Met/Met genotype and accumulation of alternative alleles in the postepidemic Fore population was indicated by the finding that the PRNP V127V synonymous substitution that showed the highest frequency in the surviving elderly women is part of the 127GG-129VV haplotype.

    “The loss of Met/Met genotype and accumulation of alternative alleles in the postepidemic Fore population was also indicated by the finding that the PRNP V127V synonymous substitution that showed the highest frequency in the surviving elderly women is part of the 127GG–129VV haplotype (38).”

    From Kuru (2012) · cites this paper as [38]

    Split into 2 atoms — 0 confirmed, 1 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • Deficit of codon 129 homozygosity was found in elderly females who lived through the epidemic in high-exposure areas and attended multiple mortuary feasts.

    “Deficit of codon 129 homozygosity was also found in analysis of elderly females who lived through the epidemic in the high-exposure areas and attended multiple mortuary feasts (38).”

    From Kuru (2012) · cites this paper as [38]

    The Hardy-Weinberg Equilibrium section reports a marked deficit of codon 129 homozygosity in elderly women from midlevel- and high-exposure zones. The Study Sample and Exposure Index section says an earlier, smaller cohort of older women had attended multiple mortuary feasts, but it does not establish that the women in the expanded high-exposure analysis had each attended multiple feasts. Page numbers are not available in our copy. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. Zigas V, 1959, Papua New Guinea Med J, 3, 1
  2. Alpers MP, 2005, Commun Dis Intell, 29, 391

Cited by

Sorted by citations

Related

Authors
Mead, S., Whitfield, J., Poulter, M., Shah, P., Uphill, J., Campbell, T., Al-Dujaily, H., Hummerich, H., Beck, J., Mein, C. A., Verzilli, C., Whittaker, J., Alpers, M. P., & Collinge, J.
Affiliations
  • MRC Prion Unit (GB)
  • Queen Mary University of London (GB)
  • London School of Hygiene & Tropical Medicine (GB)
  • Curtin University (AU)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2009-11-19
Volume
361
Issue
21
Pages
2056-2065
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa0809716
OpenAlex
W2120350230
Semantic Scholar
0c95f5a90e768e6890d50e392c5028ebafc903b7
Cited by
206
References
29
Citations by year
2026: 8 · 2025: 9 · 2024: 8 · 2023: 6 · 2022: 9 · 2021: 15 · 2020: 20 · 2019: 13 · 2018: 11 · 2017: 12 · 2016: 12 · 2015: 19 · 2014: 9 · 2013: 13 · 2012: 9
FWCI
4.80
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • eSpace (Curtin University) (submittedVersion)
Funders
  • Wellcome Trust
  • National Institute for Health and Care Research
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Amyloidosis: Diagnosis, Treatment, Outcomes
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
kuru, prion disease, PRNP gene, prion protein polymorphism, prion disease resistance, natural selection, Papua New Guinea Highlands
MeSH terms
Prion Proteins, Adolescent, Adult, Aged, Cannibalism, Disease Outbreaks, Female, Gene Frequency, Genotype, Haplotypes, Humans, Kuru, Male, Middle Aged, Papua New Guinea, Polymorphism, Genetic, Prions, Genetic Predisposition to Disease, Young Adult, Genetic Fitness

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Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-17.

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