Towards a definition of Ancient Rare Diseases (ARD): Presenting a complex case of probable Legg-Calvé-Perthes Disease from the North Caucasian Bronze Age (2200-1650 cal BCE).

OBJECTIVE: This study discusses the challenges and possibilities of establishing a definition for Ancient Rare Diseases (ARD) in a probable case of Legg-Calvé-Perthes Disease (LCPD) from the Bronze Age cemetery Kudachurt 14, situated in the Northern Caucasus. MATERIALS: We investigated the skeletal remains of a male aged 35-45 years at death. For comparison we examined other males buried at Kudachurt 14 (n = 24) and reviewed 22 LCPD cases from the paleopathological literature. METHODS: We use macroscopic as well as osteometric examination methods and imaging techniques. RESULTS: The morphology of the left hip joint corresponds to skeletal characteristics for LCPD. Co-occurring osteochondrosis dissecans, femoral anteversion, and atrophy of the left femoral shaft suggest a complex disease course. CONCLUSIONS: Modern criteria of rare diseases applied on ancient skeletal remains are either non-transferable or require completion. We conclude that rarity is dynamic, etiological uncertainty has to be accepted, and the respective socioeconomic context is crucial. Degree of disability and level of sociomedical investment are not defining criteria for ARD. SIGNIFICANCE: Dating 2200-1650 cal BCE, this study currently presents the earliest case of probable LCPD. This is the first attempt to transform modern characteristics of rare diseases for establishing a paleopathological concept of ARD. LIMITATIONS: As this study is limited to LCPD, our conclusions are not directly applicable to other ARD in question. SUGGESTIONS FOR FURTHER RESEARCH: More focused paleopathological research on skeletal populations from different cultures and time periods is needed, enabling an evolutionary perspective on the comparability of ancient, modern and future rare diseases.

Ancient human genome-wide data from a 3000-year interval in the Caucasus corresponds with eco-geographic regions.

Archaeogenetic studies have described the formation of Eurasian 'steppe ancestry' as a mixture of Eastern and Caucasus hunter-gatherers. However, it remains unclear when and where this ancestry arose and whether it was related to a horizon of cultural innovations in the 4th millennium BCE that subsequently facilitated the advance of pastoral societies in Eurasia. Here we generated genome-wide SNP data from 45 prehistoric individuals along a 3000-year temporal transect in the North Caucasus. We observe a genetic separation between the groups of the Caucasus and those of the adjacent steppe. The northern Caucasus groups are genetically similar to contemporaneous populations south of it, suggesting human movement across the mountain range during the Bronze Age. The steppe groups from Yamnaya and subsequent pastoralist cultures show evidence for previously undetected farmer-related ancestry from different contact zones, while Steppe Maykop individuals harbour additional Upper Palaeolithic Siberian and Native American related ancestry.