Genetic Susceptibility, Evolution and the Kuru Epidemic
The acquired prion disease kuru was restricted to the Fore and neighbouring linguistic groups of the Papua New Guinea highlands and largely affected children and adult women. Oral history documents the onset of the epidemic in the early twentieth century, followed by a peak in the midtwentieth century and subsequently a well-documented decline in frequency. In the context of these strong associations (gender, region and time), we have considered the genetic factors associated with susceptibility and resistance to kuru. Heterozygosity at codon 129 o the human prion protein gene (PRNP) is known to confer relative resistance to both sporadic and acquired prion diseases. In kuru, heterozygosity is associated with older patients and longer incubation times. Elderly survivors of the kuru epidemic, who had multiple exposures at mortuary feasts, are predominantly PRNP codon 129 heterozygotes and this group show marked Hardy-Weinberg disequilibrium. The deviation from Hardly-Weinberg equilibrium is most marked in elderly women, but is also significant in a slightly younger cohort of men, consistent with their exposure to kuru as boys. Young Fore and the elderly from populations with no history of kuru show Hardy-Weinberg equilibrium. An increasing cline in 129V allele frequency centres on the kuru region, consistent with the effect of selection in elevating the frequency of resistant genotypes in the exposed population. The genetic data are thus strikingly correlated with exposure. Considering the strong coding sequence conservation of primate prion protein genes, the number of global coding polymorphisms in man is surprising. By intronic resequencing in a European population, we have shown that haplotype diversity at PRNP comprises two major and divergent clades associated with 129M and 129V. Kuru may have imposed the strongest episode of recent human balancing selection, which may not have been an isolated episode in human history..
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E-Artikel |
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Erscheinungsjahr: |
2008 |
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Erschienen: |
2008 |
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Zur Gesamtaufnahme - volume:363 |
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Sprache: |
Englisch |
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Beteiligte Personen: |
Mead, Simon [VerfasserIn] |
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Biological sciences |
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PPN (Katalog-ID): |
JST065948912 |
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100 | 1 | |a Mead, Simon |e verfasserin |4 aut | |
245 | 1 | 0 | |a Genetic Susceptibility, Evolution and the Kuru Epidemic |
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520 | |a The acquired prion disease kuru was restricted to the Fore and neighbouring linguistic groups of the Papua New Guinea highlands and largely affected children and adult women. Oral history documents the onset of the epidemic in the early twentieth century, followed by a peak in the midtwentieth century and subsequently a well-documented decline in frequency. In the context of these strong associations (gender, region and time), we have considered the genetic factors associated with susceptibility and resistance to kuru. Heterozygosity at codon 129 o the human prion protein gene (PRNP) is known to confer relative resistance to both sporadic and acquired prion diseases. In kuru, heterozygosity is associated with older patients and longer incubation times. Elderly survivors of the kuru epidemic, who had multiple exposures at mortuary feasts, are predominantly PRNP codon 129 heterozygotes and this group show marked Hardy-Weinberg disequilibrium. The deviation from Hardly-Weinberg equilibrium is most marked in elderly women, but is also significant in a slightly younger cohort of men, consistent with their exposure to kuru as boys. Young Fore and the elderly from populations with no history of kuru show Hardy-Weinberg equilibrium. An increasing cline in 129V allele frequency centres on the kuru region, consistent with the effect of selection in elevating the frequency of resistant genotypes in the exposed population. The genetic data are thus strikingly correlated with exposure. Considering the strong coding sequence conservation of primate prion protein genes, the number of global coding polymorphisms in man is surprising. By intronic resequencing in a European population, we have shown that haplotype diversity at PRNP comprises two major and divergent clades associated with 129M and 129V. Kuru may have imposed the strongest episode of recent human balancing selection, which may not have been an isolated episode in human history. | ||
540 | |a Copyright 2008 The Royal Society | ||
650 | 4 | |a kuru | |
650 | 4 | |a genetics | |
650 | 4 | |a evolution | |
650 | 4 | |a Health sciences |x Medical conditions |x Diseases |x Nervous system diseases |x Central nervous system diseases |x Central nervous system infections |x Prion diseases |x Kuru | |
650 | 4 | |a Health sciences |x Medical conditions |x Diseases |x Nervous system diseases |x Central nervous system diseases |x Central nervous system infections |x Prion diseases | |
650 | 4 | |a Physical sciences |x Chemistry |x Chemical compounds |x Chemicals |x Polymers |x Biopolymers |x Proteins |x Prions | |
650 | 4 | |a Social sciences |x Population studies |x Human populations |x Persons |x Adults |x Older adults | |
650 | 4 | |a Health sciences |x Health and wellness |x Public health |x Epidemiology |x Disease outbreaks |x Epidemics | |
650 | 4 | |a Biological sciences |x Biology |x Genetics |x Molecular genetics |x Gene structures |x Nucleotide sequences |x Codons | |
650 | 4 | |a Biological sciences |x Biology |x Genetics |x Genotypes | |
650 | 4 | |a Health sciences |x Medical conditions |x Diseases |x Nervous system diseases |x Central nervous system diseases |x Neurological disorders |x Brain disorders |x Encephalopathies |x Creutzfeldt Jakob syndrome | |
650 | 4 | |a Health sciences |x Health and wellness |x Public health |x Epidemiology | |
650 | 4 | |a Biological sciences |x Biology |x Zoology |x Animals |x Mammals |x Primates |x Humans | |
650 | 4 | |a Health sciences |x Medical conditions |x Diseases |x Nervous system diseases |x Central nervous system diseases |x Central nervous system infections |x Prion diseases |x Kuru | |
650 | 4 | |a Health sciences |x Medical conditions |x Diseases |x Nervous system diseases |x Central nervous system diseases |x Central nervous system infections |x Prion diseases | |
650 | 4 | |a Physical sciences |x Chemistry |x Chemical compounds |x Chemicals |x Polymers |x Biopolymers |x Proteins |x Prions | |
650 | 4 | |a Social sciences |x Population studies |x Human populations |x Persons |x Adults |x Older adults | |
650 | 4 | |a Health sciences |x Health and wellness |x Public health |x Epidemiology |x Disease outbreaks |x Epidemics | |
650 | 4 | |a Biological sciences |x Biology |x Genetics |x Molecular genetics |x Gene structures |x Nucleotide sequences |x Codons | |
650 | 4 | |a Biological sciences |x Biology |x Genetics |x Genotypes | |
650 | 4 | |a Health sciences |x Medical conditions |x Diseases |x Nervous system diseases |x Central nervous system diseases |x Neurological disorders |x Brain disorders |x Encephalopathies |x Creutzfeldt Jakob syndrome | |
650 | 4 | |a Health sciences |x Health and wellness |x Public health |x Epidemiology | |
650 | 4 | |a Biological sciences |x Biology |x Zoology |x Animals |x Mammals |x Primates |x Humans | |
655 | 4 | |a research-article | |
700 | 1 | |a Whitfield, Jerome |e verfasserin |4 aut | |
700 | 1 | |a Poulter, Mark |e verfasserin |4 aut | |
700 | 1 | |a Shah, Paresh |e verfasserin |4 aut | |
700 | 1 | |a Uphill, James |e verfasserin |4 aut | |
700 | 1 | |a Beck, Jonathan |e verfasserin |4 aut | |
700 | 1 | |a Campbell, Tracy |e verfasserin |4 aut | |
700 | 1 | |a Al-Dujaily, Huda |e verfasserin |4 aut | |
700 | 1 | |a Hummerich, Holger |e verfasserin |4 aut | |
700 | 1 | |a Alpers, Michael P. |e verfasserin |4 aut | |
700 | 1 | |a Collinge, John |e verfasserin |4 aut | |
773 | 1 | 8 | |g volume:363 |g year:2008 |g number:1510 |g pages:3741-3746 |
856 | 4 | 0 | |u https://www.jstor.org/stable/20208826 |3 Volltext |
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