Population structure and migration in the Eastern Highlands of Papua New Guinea, a region impacted by the kuru epidemic.

Populations of the Eastern Highlands of Papua New Guinea (EHPNG, area 11,157 km2) lived in relative isolation from the rest of the world until the mid-20th century, and the region contains a wealth of linguistic and cultural diversity. Notably, several populations of EHPNG were devastated by an epidemic prion disease, kuru, which at its peak in the mid-twentieth century led to some villages being almost depleted of adult women. Until now, population genetic analyses to learn about genetic diversity, migration, admixture, and the impact of the kuru epidemic have been restricted to a small number of variants or samples. Here, we present a population genetic analysis of the region based on genome-wide genotype data of 943 individuals from 21 linguistic groups and 68 villages in EHPNG, including 34 villages in the South Fore linguistic group, the group most affected by kuru. We find a striking degree of genetic population structure in the relatively small region (average FST between linguistic groups 0.024). The genetic population structure correlates well with linguistic grouping, with some noticeable exceptions that reflect the clan system of community organization that has historically existed in EHPNG. We also detect the presence of migrant individuals within the EHPNG region and observe a significant excess of females among migrants compared to among non-migrants in areas of high kuru exposure (p = 0.0145, chi-squared test). This likely reflects the continued practice of patrilocality despite documented fears and strains placed on communities as a result of kuru and its associated skew in female incidence.

Kuru, the First Human Prion Disease.

Kuru, the first human prion disease was transmitted to chimpanzees by D. Carleton Gajdusek (1923⁻2008). In this review, we summarize the history of this seminal discovery, its anthropological background, epidemiology, clinical picture, neuropathology, and molecular genetics. We provide descriptions of electron microscopy and confocal microscopy of kuru amyloid plaques retrieved from a paraffin-embedded block of an old kuru case, named Kupenota. The discovery of kuru opened new vistas of human medicine and was pivotal in the subsequent transmission of Creutzfeldt⁻Jakob disease, as well as the relevance that bovine spongiform encephalopathy had for transmission to humans. The transmission of kuru was one of the greatest contributions to biomedical sciences of the 20th century.

Kuru: the first prion disease.

Kuru disease is linked with the name of D. Carleton Gajdusek and he was the first to show that this human neurodegenerative disease can be transmitted to chimpanzees and subsequently classified as a transmissible spongiform encephalopathy (TSE), or slow unconventional virus disease. It was first reported to Western world in 1957 by Gajdusek and Vincent Zigas,(1,2) and in 1975 a complete bibliography of kuru was published by Alpers et al.(3) "Kuru" in the Fore language in Papua New Guinea means to shiver from fever and cold. The disease has been found to spread through ritualistic cannibalism and is an invariably fatal cerebellar ataxia accompanied by tremor, choreiform and athetoid movements. Neuropathologically, kuru is characterized by the presence of amyloid "kuru" plaques.

Kuru and D. Carleton Gajdusek: a close encounter.

Kuru, the first human transmissible spongiform encephalopathy, was transmitted to chimpanzees by D. Carleton Gajdusek (1923-2008). In this review, I briefly summarize the history of this seminal discovery alongside its epidemiology, clinical picture, neuropathology and molecular genetics. The discovery of kuru opened new windows into the realms of human medicine and was instrumental in the later transmission of Creutzfeldt-Jakob disease as well as the prediction that bovine spongiform encephalopathy would be transmitted to humans. It was one of the greatest discoveries in biomedical sciences of the 20th century.

Mechanisms of sex difference: a historical perspective.

OBJECTIVE: The history of the discovery of mechanisms contributing to sex difference helps to better appreciate gender factors in a variety of disease states. The objective of this article is to illustrate four mechanisms of sex differences in disease incidence: X-linkage (including inactivation, escape from inactivating, skewed inactivation), sex-specific exposure to disease-producing pathogens, fetal microchimerism, and iron depletion. METHODS: This is a historic review. RESULTS: An emphasis on sex difference led to the uncovering of four different mechanisms by which illness rates differ in men and women. CONCLUSIONS: Research into many disease states can benefit from a focus on potential mechanisms that yield sex differences in illness susceptibility, progression, and outcome.